Head and Neck 2024-06-21

What is the force required to treat trismus in patients undergoing oral cavity free flap reconstruction?

Emma Charters, Jamie Loy, Kai Cheng, Masako Dunn, Timothy Manzie, Boyang Wan, Vinay Tumuluri, Jonathan R. Clark

Publication date 21-06-2024


Abstract Background Trismus therapy is often delayed after jaw reconstruction to avoid hardware failure or non-union. The aim of this study is to document the forces that have been applied to patients undergoing free flap reconstruction of the oral cavity in the 12 months following oral cavity reconstruction, and to analyze the associations between force and maximal interincisal opening (MIO) over time.
Methods Participants with trismus after free flap reconstruction of the oral cavity completed a 10-week jaw stretching program using Restorabite™. Primary outcome measures included the minimum and maximal force applied by a trismus device during rehabilitation, MIO, bone union, and health-related quality of life outcomes up to 12 months postoperatively.
ResultsA mean of 20.6 Newtons (N) was used during passive exercises and 38.9 N during active exercises was used during trismus therapy. The mean increase in MIO for the 45 participants after 10 weeks, 6 months, and 12 months of therapy was 8.4 mm (p < 0.001), 12.6 mm (p < 0.001), 12.7 mm (p < 0.001), respectively. There was no significant difference in the mean minimal (p = 0.37) or mean maximal (p = 0.08) force applied between those who underwent osseous free flap reconstruction compared to fasciocutaneous only, respectively. In patients who underwent osseous reconstruction, 25 (67.6%) had complete bone union and 12 (32.4%) had partial union at 12 months postsurgery.
Conclusions In participants undergoing osseous free flap reconstruction, there was no association between the force applied to the rates of bone union. Further research to define safe and optimal loading may benefit patients undergoing jaw reconstruction.

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Clinical outcomes in perineural spread of cutaneous squamous cell carcinoma via the ophthalmic nerve

Lachlan Crawford, James Bowman, Mitesh Gandhi, Sandro V. Porceddu, Benedict Panizza

Publication date 20-06-2024


Abstract Background There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines.
Objective To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1.
Materials and methods Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow-up closure date was September 1, 2021. Curative-intent surgery, curative-intent radiotherapy, or palliative care was undertaken. Endpoints included five-year overall, disease-specific, and disease-free survival from the date of treatment.
Results Five-year Kaplan–Meier overall survival was 61.9% (95% CI 46.2%–74.3%), with disease-specific survival of 74.6% (95% CI 58.8%–85.3%), and disease-free survival 62.1% (95% CI 46.5%–74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease-specific survival of 94.1% at 5 years with 82.5% disease-free survival.
Discussion Five-year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative-intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival.
Conclusion Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1.

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Systematic review of adherence to swallow and trismus exercises during radiation therapy for head and neck cancer

Emma Charters, Virginia Ricketts, Ashleigh R. Sharman, Jonathan Clark

Publication date 19-06-2024


Abstract Understanding the barriers and facilitators for prophylactic swallowing and trismus exercises for patients undergoing radiation to the head and neck may help exercise adherence. The analysis reviews all published reports of exercise adherence with a critical appraisal following PRISMA guidelines. A total of 137 potential papers were identified; 20 studies met the inclusion criteria. The most commonly reported facilitators for swallowing and trismus exercises were regular clinician contact and online resources to reinforce instructions, set goals, and manage radiation toxicities. Social support and perceived benefit from exercises were also reported to be of help. The most common barriers to exercise were radiation toxicities, anxiety, feeling overwhelmed with information, and not understanding the reason for the exercises. Understanding facilitators and barriers to adherence is critical when designing exercise interventions for patients undergoing radiation for head and neck cancer.

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A pretreatment multiparametric MRI‐based radiomics‐clinical machine learning model for predicting radiation‐induced temporal lobe injury in patients with nasopharyngeal carcinoma

Li Wang, Ting Qiu, Jiawei Zhou, Yinsu Zhu, Baozhou Sun, Guanyu Yang, Shengfu Huang, Lirong Wu, Xia He

Publication date 18-06-2024


Abstract Background To establish and validate a machine learning model using pretreatment multiparametric magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).
Methods Data from 230 patients with NPC who received IMRT (130 with RTLI and 130 without) were randomly divided into the training (n = 161) and validation cohort (n = 69) with a ratio of 7:3. Radiomics features were extracted from pretreatment apparent diffusion coefficient (ADC) map, T2-weighted imaging (T2WI), and CE-T1-weighted imaging (CE-T1WI). T-test, spearman rank correlation, and least absolute shrinkage and selection operator (LASSO) algorithm were employed to identify significant radiomics features. Clinical features were selected with univariate and multivariate analyses. Radiomics and clinical models were constructed using multiple machine learning classifiers, and a clinical-radiomics nomogram that combined clinical with radiomics features was developed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical-radiomics nomogram.
ResultsA total of 5064 radiomics features were extracted, from which 52 radiomics features were selected to construct the radiomics signature. The AUC of the radiomics signature based on multiparametric MRI was 0.980 in the training cohort and 0.969 in the validation cohort, outperforming the radiomics signature only based on T2WI and CE-T1WI (p < 0.05), which highlighted the significance of the DWI sequence in the prediction of temporal lobe injury. The area under the curve (AUC) of the clinical model was 0.895 in the training cohort and 0.905 in the validation cohort. The nomogram, which integrated radiomics and clinical features, demonstrated an impressive AUC value of 0.984 in the validation set; however, no statistically significant difference was observed compared to the radiomics model. The calibration curve and decision curve analysis of the nomogram demonstrated excellent predictive performance and clinical feasibility.
Conclusions The clinical-radiomics nomogram, integrating clinical features with radiomics features derived from pretreatment multiparametric MRI, exhibits compelling predictive performance for RTLI in patients diagnosed with NPC.

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Prognostic implications of mucosal and deep margin distances according to T‐status in oral tongue squamous cell carcinoma: A single‐center retrospective study

Valentine Poissonnet, Bertille Segier, Raphaël Lopez, Aurore Siegfried, Agnès Dupret‐Bories, Jérôme Sarini, Vinciane Poulet, Franck Delanoë, Sébastien Vergez, Emilien Chabrillac

Publication date 17-06-2024


Abstract Objective To elucidate the prognostic implications of mucosal and deep margin distances in oral tongue squamous cell carcinoma (OTSCC), and to assess a different margin cut-off value in T1-T2 versus T3-T4 tumors.
Methods This single-center retrospective study included 223 patients who received surgery for a primary OTSCC between January 2017 and December 2021.
Results Multivariable analysis showed that deep margin distance ≥3 mm in T1-T2 tumors and ≥5 mm in T3-T4 tumors was significantly associated with better RFS and OS. Mucosal and deep margin distances were globally clinically useful for 2-year RFS prediction of T1-T2 tumors, for which deep margins seemed to have more clinical utility than mucosal margins. The influence of margin distances on 2-year RFS seemed greater for T1-T2 tumors than T3-T4 tumors.
Conclusion Mucosal and deep margin distances were associated with OS and RFS in OTSCC. Shorter deep margin distances may be aimed for in T1-T2 versus T3-T4 tumors.

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Feasibility of the enhanced neuromuscular blockade recovery protocol with selective use of sugammadex in thyroid surgery with intraoperative neuromonitoring

Shuwen Yang, Zhirong Sun, Changming Zhou, Wenjun Wei, Ning Qu, Rongliang Shi, Ben Ma, Weibo Xu, Qinhai Ji, Jun Zhang, Yu Wang

Publication date 15-06-2024


Abstract Background To investigate feasibility of utilizing enhanced neuromuscular blocking agents with selective recovery protocol during thyroid surgery with intraoperative neuromonitoring (IONM).
Methods Two-hundred and ninety patients were randomized into two groups: group A 0.3 mg/kg rocuronium and group B 0.6 mg/kg. Sugammadex 2 mg/kg was injected if needed followed initial vagal stimulation (V0). Electromyography signals from vagus and recurrent laryngeal nerves before and after resection were recorded as V1, V2, R1, and R2.
Results In group B, 30 patients (20.7%) had V0 signals <100 μV, compared to 9 (6.2%) in group A. After sugammadex administration, 144 patients (99.3%) in both groups achieved positive V1 signals. Group B demonstrated a shorter surgical time from rocuronium injection to V2 stimulation compared to group A, accompanied by a significantly lower incidence of intraoperative body movement (0 vs. 16 patients).
Conclusions0.6 mg/kg rocuronium with selective use 2 mg/kg sugammadex for IONM in thyroid surgery can meet both anesthesia and surgery demands.

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Self‐management intervention improves patient adherence to swallowing exercises during radiation for head and neck cancer

Eileen H. Shinn, Adam S. Garden, Minxing Chen, Karen Basen‐Engquist, Bryan Fellman, Kate Hutcheson, William H. Morrison, Susan Peterson, Liang Li

Publication date 14-06-2024


Abstract Background While preventive swallowing exercises reduce the risk of radiation-associated dysphagia in patients with head and neck cancer, strategies are needed to improve patient adherence.
Methods Before radiation, all participants were taught preventive swallowing exercises and randomized to either an adherence intervention or enhanced usual care. During radiation, all participants met twice with a speech pathologist for swallowing assessment and reinforcement of exercises. Intervention participants met weekly with a counselor in-person or by phone. At 6-week post-radiation follow-up, all participants completed a follow-up assessment of self-reported adherence, which was then corroborated with medical record documentation.
Results Newly diagnosed pharyngeal and laryngeal cancer patients without distant metastases were randomized (n = 265; 135 to intervention, and 130 to usual care). Intervention participants were more likely to adhere to exercises during radiation compared to the control group (p < 0.0001).
Conclusion The weekly in-person adherence intervention program significantly increased patients adherence to preventive swallowing exercises during radiation.

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Squamous cell carcinoma of ear and temporal bone: A retrospective study on clinicopathological predictors

Wei Li, Bronwyn Tucker, Zhan‐Dong Hu, Yu‐Jie Zhang, Xue‐Xi Guo, Wen‐Juan Cai, Ming‐Fang Zhang, Ya‐Ting Han

Publication date 12-06-2024


Abstract Background Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China.
MethodsA cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index.
Results Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval CI = 39–64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model.
Conclusion We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.

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Timing of postoperative radiation therapy for major salivary gland cancers

Flora Yan, Jeffrey C. Liu, Rebecca Shulman, Thomas J. Galloway, John A. Ridge, Christopher M. K. L. Yao

Publication date 12-06-2024


Abstract Background The impact of timing of PORT initiation for major salivary gland cancers on survival is unknown. We aim to examine the impact of PORT timeliness on overall survival (OS) of patients with major salivary gland cancers.
Methods This was a cross-sectional analysis using data from the National Cancer Database (2004–2017) and included patients with major salivary gland cancer treated with surgery and PORT.
Results In total, 5701 patients were included (3133 55% male, 4644 82% white, mean age 59 ± 16 years). For the overall cohort, PORT >6 weeks was not associated with decreased OS (1.00 aHR, 95% CI 0.89–1.11). When specifically examining patients with mucoepidermoid carcinoma, PORT >6 weeks was associated with a decreased OS (1.27 aHR, 95% CI 1.01–1.58).
Conclusions Overall, this analysis did not demonstrate a survival benefit for initiating PORT within 6 weeks for patients with salivary gland malignancies. Subset analysis did support initiating PORT within 6 weeks after resection for patients with mucoepidermoid carcinomas. This was not demonstrated in other major salivary gland cancer histologies.

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A double‐blind randomized clinical trial of inflammatory cytokine and pepsin levels in the saliva of patients with voice prostheses

Michał Żurek, Małgorzata Czesak, Monika E. Czerwińska, Daria Berezovska, Kazimierz Niemczyk, Anna Rzepakowska

Publication date 12-06-2024


Abstract Background Tracheoesophageal speech is one of the most effective method used for voice rehabilitation after laryngectomy. The main limitation is the need for periodic voice prothesis (VP) replacements. The process of developing VP usage complications is still unexplored. The aim of this study was to assess the level of cytokines (IL-1β, IL-6, IL-8, IL-10, TNFα) and pepsin in saliva as potential factors reducing VP longevity.
Methods Prospective double-blind randomized clinical trial was conducted (NCT04268459). Patients were randomly divided into two groups depending on VP replacement regimen (regular—every 3 months, or irregular—when complications occur). Levels of IL-1β, IL-6, IL-8, IL-10, TNFα, and pepsin in saliva samples (fasting and after eating) of laryngectomized patients were measured using ELISA tests.
Results Fifty-two patients (26 in both groups) with control group (7 patients) participated in the study. The level of IL-1β, IL-6, IL-8, IL-10, TNFα, and pepsin did not differ according to regularity of VP replacements (p = 0.301–0.801). IL-6 levels were significantly higher when VP complications occurs (p = 0.012).
Conclusions The saliva components were not significantly different depending on the frequency of VP replacements. IL-6 plays an important role in the development of VP use complications.

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Detection of oral cancer and oral potentially malignant disorders using artificial intelligence‐based image analysis

Atsumu Kouketsu, Chiaki Doi, Hiroaki Tanaka, Takashi Araki, Rina Nakayama, Tsuguyoshi Toyooka, Satoshi Hiyama, Masahiro Iikubo, Ken Osaka, Keiichi Sasaki, Hirokazu Nagai, Tsuyoshi Sugiura, Kensuke Yamauchi, Kanako Kuroda, Yuta Yanagisawa, Hitoshi Miyashita, Tomonari Kajita, Ryosuke Iwama, Tsuyoshi Kurobane, Tetsu Takahashi

Publication date 11-06-2024


Abstract Background We aimed to construct an artificial intelligence-based model for detecting oral cancer and dysplastic leukoplakia using oral cavity images captured with a single-lens reflex camera.
Subjects and methods We used 1043 images of lesions from 424 patients with oral squamous cell carcinoma (OSCC), leukoplakia, and other oral mucosal diseases. An object detection model was constructed using a Single Shot Multibox Detector to detect oral diseases and their locations using images. The model was trained using 523 images of oral cancer, and its performance was evaluated using images of oral cancer (n = 66), leukoplakia (n = 49), and other oral diseases (n = 405).
Results For the detection of only OSCC versus OSCC and leukoplakia, the model demonstrated a sensitivity of 93.9% versus 83.7%, a negative predictive value of 98.8% versus 94.5%, and a specificity of 81.2% versus 81.2%.
Conclusions Our proposed model is a potential diagnostic tool for oral diseases.

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Prognostic utility of the geriatric nutritional risk index for head and neck cancer: Systematic review and meta‐analysis

Yao‐Te Tsai, Liang‐Tseng Kuo, Yun‐Ting Wang, Andrea De Vito, Sheng‐Po Hao, Ku‐Hao Fang, Yi‐Chan Lee, Kuan‐Yin Chen, Chia‐Hsuan Lai, Yuan‐Hsiung Tsai, Ethan I. Huang, Ming‐Shao Tsai, Cheng‐Ming Hsu, Geng‐He Chang, Chih‐Wei Luan

Publication date 09-06-2024


Abstract We conducted a systematic review of the literature to assess the potential prognostic utility of geriatric nutritional risk index (GNRI) for head and neck cancer (HNC). We selected studies and extracted data after searching the Cochrane Library, EMBASE, and Pub Med databases. The associations between GNRI and survival outcomes were explored by calculating hazard ratios (HRs) and 95% confidence intervals (CIs) through a random-effects meta-analysis. We included 11 studies that involved 2887 patients with HNC. The combined HR demonstrated significant associations of low GNRI with unfavorable progression-free survival (HR = 1.87, 95% CI = 1.32–2.65, p < 0.001) and overall survival (HR = 3.04, 95% CI = 2.30–4.03, p < 0.001). The association between the GNRI and overall survival persisted across various subgroups. The GNRI could serve as a valuable prognostic biomarker for patients with HNC. Low GNRI scores are significantly associated with unfavorable survival outcomes.

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Development and external validation of a head and neck cancer risk prediction model

Craig D. L. Smith, Alex D. McMahon, Donald M. Lyall, Mariel Goulart, Gareth J. Inman, Al Ross, Mark Gormley, Tom Dudding, Gary J. Macfarlane, Max Robinson, Lorenzo Richiardi, Diego Serraino, Jerry Polesel, Cristina Canova, Wolfgang Ahrens, Claire M. Healy, Pagona Lagiou, Ivana Holcatova, Laia Alemany, Ariana Znoar, Tim Waterboer, Paul Brennan, Shama Virani, David I. Conway

Publication date 08-06-2024


Abstract Background Head and neck cancer (HNC) incidence is on the rise, often diagnosed at late stage and associated with poor prognoses. Risk prediction tools have a potential role in prevention and early detection.
Methods The IARC-ARCAGE European case–control study was used as the model development dataset. A clinical HNC risk prediction model using behavioral and demographic predictors was developed via multivariable logistic regression analyses. The model was then externally validated in the UK Biobank cohort. Model performance was tested using discrimination and calibration metrics.
Results1926 HNC cases and 2043 controls were used for the development of the model. The development dataset model including sociodemographic, smoking, and alcohol variables had moderate discrimination, with an area under curve (AUC) value of 0.75 (95% CI, 0.74–0.77); the calibration slope (0.75) and tests were suggestive of good calibration. 384 616 UK Biobank participants (with 1177 HNC cases) were available for external validation of the model. Upon external validation, the model had an AUC of 0.62 (95% CI, 0.61–0.64).
Conclusion We developed and externally validated a HNC risk prediction model using the ARCAGE and UK Biobank studies, respectively. This model had moderate performance in the development population and acceptable performance in the validation dataset. Demographics and risk behaviors are strong predictors of HNC, and this model may be a helpful tool in primary dental care settings to promote prevention and determine recall intervals for dental examination. Future addition of HPV serology or genetic factors could further enhance individual risk prediction.

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Parotidectomy for deep lobe pleomorphic adenomas is associated with higher rates of complications and recurrence

Helena Levyn, Tejas Subramanian, Alana Eagan, Nora Katabi, Johanna Goldberg, Daniel W. Scholfield, Giovanna L. Caxeiro, Richard J. Wong, Marc A. Cohen, Jatin P. Shah, Snehal G. Patel, Ian Ganly

Publication date 08-06-2024


Abstract Background Pleomorphic adenoma (PA) is a common parotid tumor, yet due to the relative rarity of deep lobe PA (DLPA), there is a paucity of information about its clinical presentation and surgical outcomes.
Methods We reviewed the charts of patients with previously untreated parotid PA between the years 1990 and 2015. Clinical parameters and surgical outcomes were compared between superficial lobe PA (SLPA) and DLPA.
Results The cohort comprised 147 cases of DLPA and 222 cases of SLPA. DLPA were larger (median 2.6 cm vs. 2.0 cm, p < 0.001), more often discovered incidentally on imaging (33%, n = 48) and had unique presentations (pharyngeal mass, dysphagia, otalgia). Postsurgical complications were more frequently observed in DLPA (41% vs. 30% in SLPA, p = 0.025), mainly transient facial nerve weakness. DLPA also showed higher recurrence rates (n = 6, 4.1% vs. n = 1, 0.4%, p = 0.016).
Conclusions Parotidectomy for DLPA carries a higher risk of complications and recurrence compared to SLPA.

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Tumor desmoplasia outperforms preoperative serum calcitonin as surgical biomarker in sporadic medullary thyroid cancer

Andreas Machens, Kerstin Lorenz, Claudia Bensch, Claudia Wickenhauser, Henning Dralle

Publication date 08-06-2024


Abstract Background Conceptually, thyroid tumor desmoplasia may be better suited for excluding node metastases in sporadic MTC than preoperative serum calcitonin levels.
Methods This analysis included 181 patients with unilateral sporadic MTC graded on the 7-grade desmoplasia scale after thyroidectomy and neck dissection.
Results When thyroid tumor desmoplasia reached 1% and ≥50%, node metastases increased from 0% to 7% (median of 0 metastases) and 83% (median of 7.5 metastases), microscopic lymphatic invasion from 0% to 3% and 35%, extrathyroid extension from 0% to 5% and 22%, and extranodal growth from 0% to 0% and 44%, whereas biochemical cure declined from 100% to 95% and 25%.
Thyroid tumor diameters and basal calcitonin overlapped widely among the seven desmoplasia groups, precluding differentiation by thyroid tumor size or serum calcitonin levels.
Conclusions Thyroid tumor desmoplasia, unlike serum calcitonin levels, discriminates extremely well between node-negative and node-positive sporadic MTC, opening new avenues for precision surgery.

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Efficacy of submental island flap closing advanced mandibular MRONJ lesion in malignancy patients

Hongyuan Huang, Qiao Qiao, Ning Zhao, Ying Zhou, Yiwen Zou, Qingxiang Li, Siyuan Li, Biao Zhou, Yi Zhang, Chuanbin Guo, Yuxing Guo

Publication date 08-06-2024


Abstract Objective This study evaluated the effectiveness of a submental island flap in closing advanced mandibular medication-related osteonecrosis of the jaw (MRONJ) wounds in patients with malignant tumors.
Subjects and methodsA total of 85 patients with stage II and III MRONJ of mandible with malignant tumor as their primary disease were retrospectively analyzed. All patients underwent surgical treatment, and the soft tissue wound closure was performed either with a submental island flap (SIF) or mucoperiosteal flap (MF). Univariate and multifactorial models were applied to analyze the factors influencing patients prognosis.
Results Univariate analysis (p = 0.004, OR 0.075–0.575, 95% CI) and binary logistic regression (p = 0.017, OR 0.032–0.713, 95% CI) suggested that the surgical prognosis of SIF wound closure was significantly better than that of MF.
Conclusion Closure of wound after resection of mandibular MRONJ lesions in patients with malignant tumors using SIF had a better clinical prognosis compared with MF.

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Free fibula mandible reconstruction for osteoradionecrosis is more challenging than for primary cancer

Z‐Hye Lee, John W. Shuck, Rene D. Largo, Edward I. Chang, Matthew M. Hanasono, Peirong Yu, Patrick B. Garvey

Publication date 07-06-2024


Abstract Introduction Osteoradionecrosis (ORN) of the mandible is an unfortunate potential sequela of radiotherapy for head and neck cancer. In advanced cases of ORN, mandibulectomy, and free fibula flap reconstruction are required. We hypothesized that patients undergoing fibula free flap reconstruction and mandibulectomy for ORN pose unique challenges and experience more complications than patients undergoing fibula free flaps after oncologic mandibulectomy.
Methods After IRB approval, we created a database of all free fibula flaps for mandible reconstruction from April 2005 through February 2019. Medical records were retrospectively reviewed for patient and surgical characteristics and postoperative outcomes.
Results Four-hundred seventy-nine patients met the inclusion criteria (168 ORN vs. 311 non-ORN patients). Propensity-matching was performed based on age, BMI, smoking status, preoperative chemotherapy, and virtual surgery planning use, which yielded 159 patients in each group. ORN patients received more double-skin-island fibula flaps than non-OR patients (20.8% vs. 5.7%, p < 0.001). Recipient artery other than the facial artery was utilized more commonly in ORN patients (42.1% vs. 17.0%, p < 0.001). In the unmatched cohort, ORN patients had higher rates of delayed wound healing (26.2% vs. 16.8%, p = 0.01) and surgical site infections (21.4% vs. 13.2%, p = 0.02). Rates of flap loss, return to the operating room, hematoma, operative time, and length of stay were similar between the groups. On logistic regression analysis, osteoradionecrosis was an independent risk factor for delayed wound healing.
Conclusion Based on these data, mandibular reconstruction with fibula flaps for osteoradionecrosis appears more complicated than mandible reconstruction following de novo cancer resection. Surgeons should anticipate employing two skin islands for intraoral and extraoral resurfacing, utilizing unconventional recipient vessels, and managing the delayed wound healing that ensues more commonly than non-ORN patients.

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Microvascular reconstruction of midface osteoradionecrosis

Larissa Sweeny, Neeraja Konuthula, Ryan Jackson, Mark K. Wax, Joseph M. Curry, Sara Yang, Dev Amin, Anne C. Kane, Steve B. Cannady, Kendall Tasche, Michael DiLeo, Daniel Lander, Alexandra E. Kejner, Patrik Pipkorn

Publication date 07-06-2024


Abstract Background Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population.
Methods Retrospective multi-institutional review of FF reconstruction for midface ORN (2005–2022; n = 54).
Results The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02).
Conclusion In this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.

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Development of a plant‐based surgical training model for fluorescence‐guided cancer surgery

Mayu Shigeyama, Naoki Nishio, Akihisa Wada, Sohei Mitani, Gaku Morimoto, Sayaka Yokoi, Nobuaki Mukoyama, Mai Yokoi, Stan van Keulen, Eben Rosenthal, Michihiko Sone

Publication date 06-06-2024


Abstract Background Fluorescence-guided surgery (FGS) can help surgeons to discriminate tumor tissue from adjacent normal tissues using fluorescent tracers.
Methods We developed a surgical training model, manufactured using sustainable vegetable organic material with indocyanine green (ICG)-containing “tumor.” Surgeons evaluated the model with both the closed-field and endoscopic fluorescence imaging devices and assessed its efficacy to identify residual tumor after enucleation using electrocautery.
Results Strong correlations of fluorescence were obtained at all working distance (3, 5, 7, and 10 cm), showing the robustness of fluorescence signal for the closed-field and endoscopic fluorescence imaging devices. The higher fluorescence signals were obtained in the wound bed in the closed-field fluorescence imaging device and the residual tumor could be clearly identified by fluorescence endoscopy.
Conclusions Our FGS training model may provide experience for surgeons unfamiliar with optical surgery and subsequent tissue interactions. The model seemed particularly helpful in teaching surgeons the principles of FGS.

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The role of upfront neck dissection in definitive radiotherapy for locally advanced hypopharyngeal squamous cell carcinoma: A single‐center retrospective analysis

Atsuto Katano, Hideomi Yamashita

Publication date 06-06-2024


Abstract Background Hypopharyngeal cancer, constituting 3%–5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5-year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma.
Methods This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions.
The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND-dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate.
Results This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND-dRT groups. The 3-year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND-dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control.
Conclusion This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well-designed prospective multicenter trials.

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Correction to “Salvage total laryngectomy for squamous cell carcinoma of the larynx and hypopharynx: Validated prognostic nomograms predicting oncological outcomes”

Publication date 05-06-2024


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Reverse flow anterolateral thigh free flap in a case with significant atherosclerosis: A viable alternative for arterial microvascular anastomosis

Jonathan C. Garneau, Rod Rezaee

Publication date 04-06-2024


Abstract Background The concept of reserve flow perfusion for free flap reconstruction has been demonstrated in various applications in the literature. As it relates to the anterolateral thigh (ALT) free flap, the reserve flow principle has been primarily described to either augment or “supercharge” a large ALT to optimize skin perforator supply or lengthen the vascular pedicle.
Methods We report a case of a 77-year old male with chronic renal failure who had extensive atherosclerosis of the proximal descending lateral circumflex femoral artery (LCFA) where arterial anastomosis was unable to be performed.
Results We were able to circumvent this limitation by establishing reserve flow perfusion solely through the distal end of the descending LCFA. We describe our technique within the context of current literature on the topic of reverse flow perfusion in free flap reconstruction.
Conclusion This report uniquely describes applying the distally based, reverse arterial flow principle in an ALT flap to circumvent an atherosclerotic proximal pedicle.

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Innovative surgical approach for trigeminal trophic syndrome: Successful healing of facial ulcers through cross‐face nerve grafts

Qing Sun, Xing Li, Zhihui Zhu, Xiting Xiang, Shu Zhang, Xiaowei Liu, Xiao Long, Tao Zhang

Publication date 04-06-2024


Abstract Background Trigeminal trophic syndrome (TTS) is a rare condition caused by damage to the trigeminal nervous system, resulting in sensory disturbances and ulcers on the face. Treating TTS is complex and often requires medical or surgical intervention like flap reconstruction. However, there is limited research on surgical treatments for TTS ulcers.
Methods We report the case of a 19-year-old man with TTS. We employed an innovative surgical technique involving dual cross-face nerve grafts. In the initial procedure, corneal neuralization was accomplished using supraorbital and cross-face infraorbital nerve graft. The subsequent operation utilized auricular composite tissue flap transplantation repair and cross-face mental nerve graft.
Results This procedure led to rapid and sustained healing, as well as aesthetic improvement.
Conclusion Cross-face nerve grafts is a promising tool in the treatment of refractory ulcers caused by diseases such as TTS.

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Issue Information

Publication date 04-06-2024


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Front Cover

Austin B. Miller, Ethan Frank, Alfred A. Simental Jr, Max Feng

Publication date 04-06-2024


The cover image is based on the Original Article Surgery for nonlocalizing hyperparathyroidism in high volume center by Austin B. Miller MD et al., https://doi.org/10.1002/hed.27686.

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Analysis of local, regional, and distant recurrence of disease in mucoepidermoid tumors of larynx: A systematic review

Francesco Chiari, Giuseppe Di Martino, Claudio Donadio Caporale, Gabriele Molteni, Livio Presutti, Pierre Guarino

Publication date 04-06-2024


Abstract The aim of this systematic review is to analyze epidemiology, clinical presentation, histopathological features, treatment and oncological outcomes in laryngeal mucoepidermoid cancer (MEC) in order to improve the knowledge on the management of such a rare malignant neoplasm. Specifically, authors highlight patients and tumors features about local, regional, and distant recurrence of disease. PRISMA 2020 guidelines were applied in this systematic literature review. A computerized search was performed using the Embase/Pubmed, Scopus, and Cochrane databases, for articles published from 1971 to December 2023. A descriptive and univariate analysis including selected papers with low or intermediate risk of bias was performed. Twenty-seven papers (11 case series and 16 case reports) were included in this review. Fifty-six patients were included in the analyses, with a mean age of 56.7 years; 84% of them were males. Most patients (86%) underwent a primary surgical approach.
Clinical stage was reported as follows: early stage (26 patients) and locally advance and advanced stage (19 patients). Overall survival (OS) and disease-free survival (DFS) at 2 years was 80% and 78%, respectively. The mean time to local recurrence was 18.7 months (range 8–36 months). The survival after recurrence is about 85% and 70% at 5 years, respectively. The mean time of lymph node recurrence was 14.7 months (range 7–19 months). Finally, the mean time of distant recurrence was 15 months (range 7–36 months) with a poor prognosis: all patients died due to the disease in a range of 0–7 months after metastasis evidence. Laryngeal MEC is a rare neoplasm of minor salivary glands in the larynx. No guidelines or indications about the management of this neoplasm are reported in the literature. The lower incidence of regional recurrence of the disease and the better OS and DFS underline how the prognosis of MEC is more favorable respect to other malignant histotypes.

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Reply to Letter to the Editor regarding “Decreased utilization for postoperative radiation therapy in locoregionally advanced medullary thyroid cancer”

Anastasios Maniakas, Mimi I. Hu, G. Brandon Gunn, Mark Zafereo

Publication date 04-06-2024


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Evidence for postoperative radiotherapy in medullary thyroid cancer

N. P. Rowell

Publication date 04-06-2024


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Surgery for nonlocalizing hyperparathyroidism in high volume center

Austin B. Miller, Ethan Frank, Alfred A. Simental Jr, Max Feng

Publication date 04-06-2024


Abstract Background Patients with nonlocalizing hyperparathyroidism pose a significant challenge to surgeons when undergoing neck exploration for parathyroidectomy.
Methods We evaluated 536 patients that had parathyroidectomy for primary hyperparathyroidism (PHPT) from 2005 to 2018 at a single tertiary academic center, and 155 (29%) had standard nonlocalizing preoperative imaging (negative ultrasound and sestamibi scans).
Results There were a total of 102 (66%) non-ectopic single adenomas in the nonlocalizing group and 325 (85%) single adenomas in the localizing group. There was no significant difference (p = 0.09) in adenoma quadrant between localizing and nonlocalizing single adenomas, but the most common location in both groups was right inferior. Patients with nonlocalizing scans were more likely to have double adenomas (21% vs. 9%, p < 0.001), ectopic glands (10% vs. 5%, p = 0.052), and multi-gland disease (13% vs. 8%, p = 0.002).
Conclusion Nonlocalizing PHPT patients experienced similar cure and complication rates as localizing PHPT, but required more bilateral explorations and increased operative time.

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Weekly assessment of volumetric and dosimetric changes during volumetric modulated arc therapy of locally advanced head and neck carcinoma: Implications for adaptive radiation therapy—A prospective study

Aathira T. Sreejeev, Deepa Joseph, Ajay S. Krishnan, Rajesh Pasricha, Sweety Gupta, Rachit Ahuja, Nidhi Sharma, Debanjan Sikdar, Sagar Raut, Abhijith Sasi, Manoj Gupta

Publication date 04-06-2024


Abstract Background Chemoradiation in head and neck carcinoma (HNC) shows significant anatomical resulting in erroneous dose deposition in the target or the organ at risk (OAR). Adaptive radiotherapy (ART) can overcome this. Timing of significant target and OAR changes with dosimetric impact; thus, most suitable time and frequency of ART is unclear.
Methods This dosimetric study used prospective weekly non-contrast CT scans in 12 HNC patients (78 scans). OARs and TVs were manually contoured after registration with simulation scan. Dose overlay done on each scan without reoptimization. Dosimetric and volumetric variations assessed.
Results Commonest site was oropharynx. Gross Tumor Volume (GTV) reduced from 47.5 ± 19.2 to 17.8 ± 10.7 cc. Nodal GTV reduced from 15.7 ± 18.8 to 4.7 ± 7.1 cc. Parotid showed mean volume loss of 35%. T stage moderately correlated with GTV regression.
Conclusion Maximum GTV changes occurred after 3 weeks. Best time to do single fixed interval ART would be by the end of 3 weeks.

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Telemedicine‐enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma

Douglas B. Chepeha, Carly E. A. Barbon, Alex O. Esemezie, Majd Al Mardini, Justine Philteos, Matthew E. Spector, Tim Bressmann, Rosemary Martino, Scott V. Bratman, John B. C. Cho, Andrew J. Hope, Ali Abdalati Hosni, John J. H. Kim, Jolie G. Ringash, John N. Waldron, Dale H. Brown, John R. de Almeida, Ralph W. Gilbert, David P. Goldstein, Patrick J. Gullane, Jonathan C. Irish, Eric A. Monteiro, Christopher M. K. L. Yao

Publication date 04-06-2024


Abstract Background To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/− adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after “standard-of-care” SOC rehabilitation.
Method Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation.
Results Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, “range-of-liquids” improved by +0.36 95% CI, 0.02–0.70, p = 0.05 and “range-of-solids” improved by +0.73 95% CI, 0.12–1.34, p = 0.03. There was a positive trend toward better oral cavity obliteration; residual volume decreased by −1.2 95% CI, −2.45 to 0.053, p = 0.06, and “nutritional-mode” increased by +0.55 95% CI, −0.15 to 1.24, p = 0.08.
Conclusion This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.

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Survival and complications after carotid resection for head and neck squamous cell carcinoma: A systematic review and pooled analysis

Gian Marco Pace, Carolina Morales‐Olavarría, Andrea Costantino, Bianca Maria Festa, Elena Russo, Giannicola Iannella, Claudio Carnevale, Pasquale Di Maio, Claudio Sampieri, Remo Accorona, Armando De Virgilio

Publication date 04-06-2024


Abstract Objective The aim of this study is to analyze oncologic outcomes and complications rate after common or internal carotid artery (CCA/ICA) resection for head and neck squamous cell carcinoma (HNSCC).
Methods This study was conducted in conformity with the PRISMA statement. A systematic review and pooled analysis was performed for overall survival (OS), disease specific survival (DSS) (primary outcomes), and perioperative death rate (secondary outcome).
ResultsA total of 276 patients (males: 76.7%, n = 191/249) with a median age of 59 years (n = 239/276; 95% CI 55.0–61.7) who underwent CCA/ICA resection for HNSCC were included. The median follow-up time was 11 months (n = 276). Estimated pooled OS rates (95% CI) at 1 and 2 years were 52.7% (46.9–59.2) and 29.8% (24.3–36.5), respectively. The median OS (95% CI) was 14 months (12–17). Estimated pooled DSS rates (95% CI) at 1 and 2 years were 58.6% (52.7–65.2) and 34.6% (28.5–41.9), respectively. The median DSS (95% CI) was 16 months (14–19). The perioperative death rate was 6.9% (n = 19/276).
ConclusionsCCA/ICA resection should be considered as a treatment option for accurately selected patients. Multicentric prospective studies are recommended to develop a predictive score guiding the decision-making process.

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Treatment discordance in the utilization of neck dissection for stage I‐II supraglottic tumors

Shivee Gilja, Vikram Vasan, Arvind Kumar, Scott A. Roof, Eric M. Genden, Diana N. Kirke

Publication date 04-06-2024


Abstract Background In 2018, the National Comprehensive Cancer Network treatment guidelines began recommending the use of neck dissection during surgical management of stage I-II supraglottic laryngeal squamous cell carcinoma (LSCC).
Methods Trends and factors associated with the use of neck dissection during larynx-preserving surgery for patients with cT1-2, N0, M0 supraglottic LSCC in the National Cancer Database (2004–2020) were evaluated using multivariable-adjusted logistic regression.
Results Of the 2080 patients who satisfied study eligibility criteria, 633 (30.4%) underwent neck dissection. Between 2018 and 2020, the rate of neck dissection was 39.0% (114/292). After multivariable adjustment, academic facility type, undergoing biopsy prior to surgery, and more radical surgery were significant predictors of receiving neck dissection.
Conclusions The results of this national analysis suggest that the utilization of guideline-concordant neck dissection for management of stage I-II supraglottic LSCC remains low and highlight the need to promote the practice of neck dissection for this patient population.

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Squamous cell carcinoma of the nasal vestibule in the Netherlands: A clinical and epidemiological review of 763 cases (2008–2021)

Lise J. van de Velde, W. F. Julius Scheurleer, W. Weibel Braunius, Lot A. Devriese, Mischa de Ridder, Remco de Bree, Gerben E. Breimer, Boukje A. van Dijk, Johannes A. Rijken

Publication date 04-06-2024


Abstract Background Squamous cell carcinoma of the nasal vestibule (SCCNV) is a rare disease, distinctly different in presentation, treatment, and outcome from squamous cell carcinoma (SCC) of the nasal cavity and paranasal sinuses. However, these are often not analyzed separately.
Methods The Netherlands Cancer Registry (NCR) and pathology reports from the Dutch Nationwide Pathology Databank (PALGA) were used to identify all newly diagnosed SCCNV cases in the Netherlands between 2008 and 2021.
ResultsA total of 763 patients were included. The yearly incidence rate displayed a significant downward trend with an annual percentage change (APC) of −3.9%. The 5-year overall survival (OS) and disease-free survival were 69.0% and 77.2%, respectively. The 5-year relative survival was 77.9% and improved slightly over the inclusion period. OS for patients who were staged cT3 appeared to be worse than those staged cT4a, calling the applicability of the TNM-classification into question.
ConclusionSCC of the nasal vestibule is rare, with declining incidence rates. Introducing a specific topography code for SCCNV is recommended to enhance registration accuracy. The TNM classification seems poorly applicable to SCCNV, suggesting the need to explore alternative staging methods.

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Transoral robotic surgery with free flap reconstruction: Functional outcomes of 241 patients at a single institution

Praneet C. Kaki, Doreen Lam, Neel R. Sangal, Karthik Rajasekaran, Ara C. Chalian, Robert M. Brody, Gregory S. Weinstein, Steven B. Cannady

Publication date 04-06-2024


Abstract Background Transoral robotic surgery (TORS) for oropharyngeal malignancy optimizes oncologic outcomes while preserving functionality. This study identifies patterns of functional recovery after TORS with free flap reconstruction (FFR).
Methods Retrospective cohort study at a tertiary care center of patients with primary oropharyngeal tumors treated with TORS with FFR between 2010 and 2022.
Patients were categorized into: adjuvant chemoradiation or radiation, or no adjuvant therapy (NAT). Functional outcomes were measured by functional oral intake scale (FOIS).
Results241 patients were included. FOIS declined at first postoperative appointment (median = 7.0 to 2.0, IQR = 7.0, 7.0, 2.0, 4.0), and progressively improved to 6.0 (5.0, 6.0) after 1 year, with NAT having the highest FOIS (7.0, p < 0.05). Predictors of poor long-term FOIS included RT and hypoglossal nerve (CN XII) involvement (p < 0.05).
ConclusionsTORS with FFR leads to good long-term function with minimal intake restrictions. Radiation therapy and CN XII involvement increase risk of worse functional outcomes.

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The efficacy of the National Surgical Quality Improvement Program surgical risk calculator in head and neck surgery: A meta‐analysis

Jacob Harris, Vinayak Ahluwalia, Katherine Xu, Dominic Romeo, Christian Fritz, Karthik Rajasekaran

Publication date 04-06-2024


Abstract Background The National Surgical Quality Improvement Program surgical risk calculator (SRC) estimates the risk for postoperative complications. This meta-analysis assesses the efficacy of the SRC in the field of head and neck surgery.
MethodsA systematic review identified studies comparing the SRCs predictions to observed outcomes following head and neck surgeries. Predictive accuracy was assessed using receiver operating characteristic curves (AUCs) and Brier scoring.
Results Nine studies totaling 1774 patients were included. The SRC underpredicted the risk of all outcomes (including any complication observed (ob) = 35.9%, predicted (pr) = 21.8% and serious complication ob = 28.7%, pr = 17.0%) except mortality (ob = 0.37%, pr = 1.55%). The observed length of stay was more than twice the predicted length (p < 0.02). Discrimination was acceptable for postoperative pneumonia (AUC = 0.778) and urinary tract infection (AUC = 0.782) only. Predictive accuracy was low for all outcomes (Brier scores ≥0.01) and comparable for patients with and without free-flap reconstructions.
Conclusion The SRC is an ineffective instrument for predicting outcomes in head and neck surgery.

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The novel circ_0004674/miR‐139‐5p/ZBTB2 regulatory cascade inhibits the development of oral squamous cell carcinoma

Chuang Qi, Lu Zhang, Wenping Wang

Publication date 04-06-2024


Abstract Background Circular RNAs (circRNAs) are an intriguing family of RNA molecules due to their crucial roles in the pathogenesis of oral squamous cell carcinoma (OSCC). Here, we sought to define the action of human circ_0004674 in OSCC progression.
Methods The functional role of circ_0004674 was validated by determining its effect on cell growth, apoptosis, and tube formation ability of OSCC cells. For protein quantification, a western blot or immunohistochemistry method was applied. The interaction between miR-139-5p and circ_0004674 or zinc finger and BTB domain containing 2 (ZBTB2) was predicted by online algorithms, and their relationships were confirmed by dual-luciferase reporter and RIP assays. Xenograft models were established to uncover circ_0004674s role in tumor growth.
Results Circ_0004674 expression was upregulated in OSCC. Functionally, knocking down circ_0004674 led to suppressed OSCC cell progression in vitro and delayed tumor growth in vivo. Mechanistically, circ_0004674 post-transcriptionally controlled ZBTB2 expression by competitively pairing to miR-139-5p. Furthermore, the deficiency of miR-139-5p abated circ_0004674 silencing-mediated OSCC cell progression repression, and augmentation of ZBTB2 reversed the anticancer effect of miR-139-5p on OSCC.
Conclusion Our findings uncover a novel regulatory cascade, the circ_0004674/miR-139-5p/ZBTB2 axis, with the ability to affect OSCC development in vitro and in vivo, providing a potential opportunity for development of OSCC therapy.

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Tubarial gland sparing with intensity modulated radiation therapy for oropharyngeal cancers: A pilot study of dosimetric feasibility

Sreenija Yarlagadda, Nicole McAllister, Amy E. Rzepczynski, Tugce Kutuk, Noah S. Kalman

Publication date 04-06-2024


Abstract Background Tubarial glands are a new organ at risk for head and neck cancer radiation therapy (RT). We aimed to study the feasibility of sparing them using intensity-modulated radiation therapy (IMRT).
Methods Tubarial glands were delineated for 17 patients with oropharyngeal carcinoma receiving definitive RT, and treatment plans were re-optimized to spare dose to the tubarial glands while maintaining target coverage. A paired t test was performed to compare the mean dose of tubarial glands and target coverage.
Results The difference in mean doses was 4.9 and 7.0 Gy for the ipsilateral and contralateral tubarial glands, respectively (p < 0.01). The mean dose to tubarial gland was ≤39 Gy in 35% versus 47% (ipsilateral) and 70% versus 100% (contralateral) in clinical and re-optimized plans, respectively. Re-optimized ipsilateral tubarial gland mean ≤39 Gy was achieved more commonly in patients with base of tongue versus tonsil primaries (86% vs. 20%, p = 0.02).
Conclusion This pilot study demonstrates the dosimetric feasibility of tubarial gland sparing with IMRT. Dosimetric constraints need to be determined with larger studies.

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The methodological and reporting quality of randomized controlled trials of tyrosine kinase inhibitors for advanced differentiated thyroid cancer: Meta‐research study

Rogério Aparecido Dedivitis, Mario Augusto Ferrari de Castro, Alice Matos Dal Boni, Ana Carolina Beltrão Alvares, Ana Júlia Piazentin Tresso, Andrea Davedovicz de Oliveira, Amanda Gonçalves da Silva Dourado Vieira, Fernanda Assaf Mendes, Giovana de Oliveira Rossi, Giullia Neworal Fava, Isabela Santos Pouza, Izabelle Pimenta Santana, Julia Gibran Laino, Letícia Barbosa de Lima, Ana Luiza Cabrera Martimbianco

Publication date 04-06-2024


Abstract Introduction Clinical trials on tyrosine kinase inhibitors (TKI) treatment have shown an improvement in overall and progression-free survival in patients with advanced differentiated thyroid cancer. However, it is necessary to evaluate these studies to assess methodological biases and inconsistencies that may impact the effects.
Objective To map and assess the methodological quality of randomized clinical trials (RCTs) regarding randomization, allocation concealment, blinding, and selective reporting bias.
MethodsRCTs assessing the efficacy and safety of TKI for the treatment of advanced differentiated thyroid cancer were included. The search was performed in the MEDLINE database. The included RCTs were assessed for the adequacy of the methodological steps, as recommended by the Cochrane Risk of Bias tool.
Results Nine studies were analyzed, of which 77.7% were classified as low risk of bias regarding selective reporting and 33.3% as high risk of reporting bias. The mean time between protocol registration and study publication was approximately 5.11 years. Moreover, 66.7% were classified as low risk of bias for randomization and allocation concealment, and 33.3% did not specify the randomization process and allocation concealment in a way that would allow the identification of occurrences of bias. Concerning blinding of participants and outcome assessors, 77.8% of the RCTs reported adequate blinding and were classified as having a low risk of bias, 11.1% had a high risk of bias, and 11.1% had insufficient information and were classified as having unclear risk of bias. Regarding the blinding of the outcome assessors, 33.3% did the blinding correctly, 11.1% did not blind, and 55.6% did not provide enough information.
Conclusion Overall, the assessed RCTs were predominantly at low risk of bias. The critical evaluation of these studies is essential to have confidence in the treatment estimated effect that will support clinical decision-making and provide information to preclude future clinical study flaws.

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The prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma

Peter K. M. Ku, Alexander C. Vlantis, Thomas S. C. Hui, Zenon W. C. Yeung, Ryan H. W. Cho, Marc H. K. Wong, Alex K. F. Lee, David C. M. Yeung, Simon Y. P. Chan, Becky Y. T. Chan, Wai‐tsz Chang, Florence Mok, Kam‐hung Wong, Jeffrey K. T. Wong, Victor Abdullah, Andrew van Hasselt, Justin C. Y. Wu, Michael C. F. Tong

Publication date 04-06-2024


Abstract Background The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post-irradiated patients with nasopharyngeal carcinoma (NPC) is unknown.
Materials and methods In a cross-sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24-h pH monitoring. The De Meester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified.
Results51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD-positive and LPR-positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR-positive and GERD/LPR-negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR.
ConclusionsA high prevalence of GERD/LPR in patients with post-irradiated NPC exists, but reflux symptoms are inadequate for diagnosis.

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Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma

Ester Benaiges, Victòria Ceperuelo‐Mallafré, Sandra Guaita, Elsa Maymó‐Masip, Ana Madeira, David Gómez, Victor Hernández, Isabel Vilaseca, Carla Merma, Xavier León, Ximena Terra, Joan Vendrell, Francesc Xavier Avilés‐Jurado, Sonia Fernández‐Veledo

Publication date 04-06-2024


Abstract Background Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies.
Methods We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response.
Results Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells.
Conclusions Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

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"Succinate dehydrogenase mutations in head and neck paragangliomas: A systematic review and meta‐analysis of individual patients data"

Elizabeth S. Koh, Anas Dabsha, Mohamed Rahouma, Kyle Zappi, Yashes Srinivasan, Andy Hickner, David I. Kutler

Publication date 04-06-2024


Abstract Background Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs.
Methods Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta-regression was performed. Cochrans Q test and I2 test assessed heterogeneity. Funnel plot and Eggers regression test assessed publication bias.
Results Forty-two studies with 8849 patients were included. Meta-regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH-related mutations.
Conclusion Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH-related mutations has the potential to influence the management approach to such HNPs.

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The use of customized 3D‐printed mandibular prostheses with pressure‐reducing device: A clinical trial

Chun‐Feng Chen, Chun‐Ming Chen, Wei‐Chin Huang, Sung‐Ho Liu, Ling‐Lin Wang, Pei‐Feng Liu, Ping‐Ho Chen

Publication date 04-06-2024


Abstract Background Segmental bone defects of the mandible result in the complete loss of the affected region. We had incorporated the pressure-reducing device (PRD) designs into the customized mandible prostheses (CMP) and conducted a clinical trial to evaluate this approach.
Methods Seven patients were enrolled in this study. We examined the association among the history of radiotherapy, the number of CMP regions, the number of chin regions involved, and CMP exposure.
Results We included five men and two women with an average age of 55 years. We excised tumors with an average weight of 147.8 g and the average weight of the CMP was 68.5 g. No significant difference between the two weights was noted (p = 0.3882). Three patients received temporary dentures and the CMP remained stable in all patients.
Conclusion The use of PRD in CMP may address the previous challenges associated with CMP, but further research is necessary.

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Vascular events in patients with head and neck cancer: A systematic review and meta‐analysis

Neil P. Monaghan, Kelsey A. Duckett, Shaun A. Nguyen, Jason G. Newman, W. Greer Albergotti, Alexandra E. Kejner

Publication date 04-06-2024


Abstract Objective To assess the incidence of vascular events in patients with head and neck cancer.
Review Methods Primary studies identified through April 2023. Meta-analysis was performed.
Results There were 146 studies included in the systematic review. Rates of events were collected in the overall group, those with chemoprophylaxis, and those that underwent surgery, radiation, or chemotherapy. Of 1 184 160 patients, 4.3% had a vascular event. Radiation therapy had highest risk of overall events and stroke when compared to surgery and chemotherapy. Chemotherapy had a higher risk of stroke and overall events when compared to surgery.
Conclusions Vascular events occur in 4%–5% of patients with head and neck cancer. Our data does not support the use of routine anticoagulation. Patients undergoing radiation therapy had the highest frequency of events.

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The effect of carbon nanoparticles vs. immune colloidal gold technique test strips on parathyroid protection in total thyroidectomy: A randomized clinical trial study

Bochun Wang, Yiyuan Zhu, Shiguo Zhou, Cheng Lu, Aobo Zhang, Jun Tian, Wanxin Li, Shuling Ren, Yanbo Dong, Liangfa Liu

Publication date 04-06-2024


Abstract Background The long-term effect of intraoperative usage of carbon nanoparticles (CN) and parathyroid hormone (PTH) test strip using immune colloidal gold technique (ICGT) is unclear. This study aims to compare the effect of intraoperative usage of CN and ICGT test strips on PG function.
Methods This randomized clinical study involved adult patients who underwent total thyroidectomy. They were randomly allocated into three groups (control, CN, and ICGT group). Clinical data were analyzed.
Results Each group involved 98 patients. Serum calcium and PTH concentrations at 24 h postoperatively (PTH24h) were higher in CN group. The parathyroid function recovered quicker in CN group. Use of CN increased in situ PG preservation and PTH24h. Mediation analysis indicated that 23.05% of the total effect of CN on PTH24h was attributed to PGRIS.
ConclusionCN holds promise to improve in situ PG preservation and protect PG vasculature, thereby reducing the incidence of early hypoparathyroidism. The value of ICGT test strips for PG protection is dubious.

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Various arrangements of pharyngeal flap in soft palate reconstruction after cancer treatment

Hiroshi Matsumoto, Tomoyuki Ota, Motoi Kato, Takuma Makino, Seiichiro Makihara, Mizuo Ando, Yoshihiro Kimata

Publication date 04-06-2024


Abstract Background The pharyngeal flap (PF) is useful for reconstruction of soft palate defects, but effective arrangements of PF for various types of soft palate defects are controversial. Here, we classify three types of soft palate defects and discuss the arrangements of PF and their functional prognosis.
Methods Reconstruction was performed based on the classification of the defects. Clinical details were collected, and postoperative function was analyzed.
Results Eight patients were included in the study. The defect sizes ranged from 25 (width) × 40 (depth) to 40 × 60 mm. Six patients underwent pharyngeal flap reconstruction with free-flap reconstruction, and two underwent pharyngeal flap reconstruction. The pharyngeal flap was harvested at the maximum width of the posterior pharyngeal wall, ranging from 25 to 40 mm in length. Eating and speaking functions were maintained in all patients.
Conclusions Good postoperative function can be maintained by narrowing the velopharyngeal space with a pharyngeal flap.

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The impact of COVID‐19 and vaccination status on outcomes in veterans with head and neck squamous cell carcinoma

James D. Johns, Erica J. Choe, Paul F. Chisolm, Morgan J. Pothast, Jackson R. Randolph, Jiling Chou, Jessica H. Maxwell

Publication date 04-06-2024


Abstract Background The impact of both COVID-19 infection and vaccination status on patients with head and neck squamous cell carcinoma (HNSCC) remains unknown.
Objective To determine the impact of COVID-19 infection and vaccination status on 60-day mortality, cardiovascular, and respiratory complications in patients with a prior diagnosis of HNSCC.
Methods This was a retrospective cohort study through the Veterans Affairs (VA) Corporate Data Warehouse of Veterans with HNSCC who were tested for COVID-19 during any inpatient VA medical center admission. A cohort of patients was created of Veterans with a diagnosis of HNSCC of the oral cavity,oropharynx, hypopharynx, larynx, and nasopharynx based on International Classification of Disease (ICD) codes. Data collected included clinical/demographic data, vaccination status, and incidence of 60-day mortality, 60-day cardiovascular complication (including myocardial infarction, venous thromboembolism, cerebrovascular accident), and 60-day respiratory complication (including acute respiratory failure, acute respiratory distress syndrome, and pneumonia). The interactions between COVID-19 infection, vaccination status, morbidity and mortality were investigated.
Results Of the 14 262 patients with HNSCC who were tested for COVID-19 during inpatient admission, 4754 tested positive (33.3%), and 9508 (67.7%) tested negative. Patients who tested positive demonstrated increased 60-day mortality (4.7% vs. 2.0%, respectively; p < 0.001), acute respiratory failure (ARF; 15.4% vs. 7.1%, p < 0.001), acute respiratory distress syndrome (ARDS; 0.9% vs. 0.2%, p < 0.001), and pneumonia (PNA; 20.0% vs. 6.4%, p < 0.001) compared to those who never tested positive, respectively. Patients who received COVID-19 vaccination between 2 weeks and 6 months prior to a positive test demonstrated decreased rates of ARF (13.2% vs. 16.0%, p = 0.034) and PNA (16.7% vs. 20.9%, p = 0.003) compared to the unvaccinated group. A logistic regression of patients with COVID-19 infections who died within 60 days was performed, with no significant survival advantage among patients vaccinated between 2 weeks and 6 months prior to the positive test.
ConclusionCOVID-19 infection may significantly increase rates of 60-day mortality and respiratory complications in patients with HNSCC. COVID-19 vaccination between 2 weeks and 6 months prior to infection may decrease severity of respiratory complications but did not show significant mortality benefits in this study. These data highlight the need for surveillance of respiratory infection and vaccination in this vulnerable population.

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The tumor microenvironment of benign and malignant salivary gland tumors

Katherine C. Wai, Trine Line H. Okholm, Patrick K. Ha, Diana M. Marquez, Iliana Tenvooren, Kyle B. Jones, Matthew H. Spitzer

Publication date 04-06-2024


Abstract Background Treatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs.
Methods Eleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time-of-flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high-grade and low-grade malignancies, corrected for multiple hypothesis testing.
Results There were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High-grade malignancies exhibited trends towards higher frequencies of CD8+ PD-1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF-1+ CD127− Tregs, and CD69+ CD25− CD4+ T cells compared to low-grade malignancies.
ConclusionSGTs exhibit significant immunologic diversity. High-grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies.

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The Gothenburg Trismus Questionnaire in China: Cross‐cultural adaptation and measurement invariance

Qian Zhang, Yao Feng, Ying‐Hui Zhou, Yi‐Fan Yang, Yun‐Zhi Feng, Yue Guo

Publication date 04-06-2024


Abstract Objectives The Gothenburg Trismus Questionnaire (GTQ) is a comprehensive scale for screening and assessing trismus in head and neck (H&N) cancer and temporomandibular joint disorders (TMD) patients. This study aimed to translate and cross-culturally adapt the GTQ in China, and to test its measurement invariance.
Methods This study comprised 278 H&N cancer, 245 TMD, and 507 control patients. Internal consistency and test–retest reliability were tested to assess the GTQs reliability. The validity was evaluated through composite reliability (CR), average variance extracted (AVE), and correlation tests. Multi-group confirmatory factor analysis (CFA) was used to investigate the GTQs measurement invariance across clinical status and gender. T tests were employed to compare score differences across clinical status and gender.
Results The Chinese version of GTQ scale shows excellent internal consistency and test–retest reliability. The CR, AVE, and correlation values demonstrate the good validity of GTQ. The multi-group CFA supported configural invariance across clinical status but not metric invariance, while it supported strict invariance across gender. Additionally, t tests revealed that patients with H&N cancer and TMD scored higher than the control group, while males scored higher than females.
Conclusions The Chinese version of GTQ serves as an effective tool for screening and assessing trismus.

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Survival outcomes and toxicity profiles among patients with nonmetastatic nasopharyngeal carcinoma treated with intensity‐modulated radiotherapy (IMRT) versus IMRT + carbon‐ion radiotherapy: A propensity score‐matched analysis

Yujiao Li, Xiyin Guan, Xing Xing, Chaosu Hu

Publication date 04-06-2024


Abstract Objectives To compare survival outcomes and toxic effects among patients with newly diagnosed nonmetastatic nasopharyngeal carcinoma (NPC) when treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy (CIRT).
Methods We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMRT and IMRT + CIRT. Descriptive statistics were used to examine the baseline characteristics of the patients. Survival was estimated using the Kaplan–Meier method. Univariate and multivariable logistic regression analysis were used to identify the independent predictors of survival. We examined the association between risk factors and adverse events (AEs) using chi-square tests. Cox model and logistic regression were used to analyze AEs.
Results Hundred and nine patients who received IMRT + CIRT were included and the median follow-up time was 20.6 months (range: 4.6–82 months). There were no statistically significant differences in locoregional failure–free survival, distant metastasis–free survival, disease-free survival, or overall survival between the two groups, but potentially better in IMRT + CIRT group (p > 0.05, respectively). Nodal boost was the only significant factor associated with LRFS and DFS on multivariable analysis. Thirty-seven patients (34.0%) developed grade 3 acute OMs and no grade 4 acute OMs were observed in IMRT + CIRT group. All patients in IMRT + CIRT group developed grade 1 dermatitis; while in the match group, 76 patients developed grade 1 dermatitis, 27 patients developed grade 2 dermatitis, 5 patients developed grade 3 dermatitis, 1 patient developed grade 4 dermatitis. IMRT + CIRT treatment was associated with a significant trend of lower grades of OM and dermatitis (p < 0.05, respectively). Any severe (i.e., grade 3) chronic AEs, such as xerostomia, skin fibrosis, temporal lobe necrosis, osteoradionecrosis, or radiation-induced optic neuropathy, was not observed.
Conclusions In this study, IMRT + CIRT was associated with significantly reduced acute toxicity burden compared with full course of IMRT, with excellent survival outcomes. Patients with persistent disease after treatment and treated with nodal boost had a worse outcome. More accurate assessments of IMRT + CIRT to primary nonmetastatic NPC patients will be imperative.

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The potential value of oral microbial signatures for prediction of oral squamous cell carcinoma based on machine learning algorithms

Baochang He, Yujie Cao, Zhaocheng Zhuang, Qingrong Deng, Yu Qiu, Lizhen Pan, Xiaoyan Zheng, Bin Shi, Lisong Lin, Fa Chen

Publication date 04-06-2024


Abstract Objective This study aimed to explore the potential predictive value of oral microbial signatures for oral squamous cell carcinoma (OSCC) risk based on machine learning algorithms.
Methods The oral microbiome signatures were assessed in the unstimulated saliva samples of 80 OSCC patients and 179 healthy individuals using 16S rRNA gene sequencing. Four different machine learning classifiers were used to develop prediction models.
Results Compared with control participants, OSCC patients had a higher microbial dysbiosis index (MDI, p < 0.001). Among four machine learning classifiers, random forest (RF) provided the best predictive performance, followed by the support vector machines, artificial neural networks and naive Bayes. After controlling the potential confounders using propensity score matching, the optimal RF model was further developed incorporating a minimal set of 20 bacteria genera, exhibiting better predictive performance than the MDI (AUC: 0.992 vs. 0.775, p < 0.001).
Conclusions The novel MDI and RF model developed in this study based on oral microbiome signatures may serve as noninvasive tools for predicting OSCC risk.

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Myomucosal composite graft: A simple technique for full‐thickness vermilion defects of the lower lip

Kyu‐Il Lee, Seung‐Kyu Han, Seong‐Ho Jeong, Eun‐Sang Dhong

Publication date 04-06-2024


Abstract Reconstruction of vermillion defects of the lower lip requires careful consideration of functional and aesthetic aspects. Traditionally, various local flap methods involving tissue advancement from the corner of the mouth, lateral chin, and medial cheek have been commonly employed to fill lower lip defects. However, these approaches have inherent limitations, which include technical complexity, disruption of the orbicularis oris muscle, lip tightening, microstomia, and visible scarring. To overcome these limitations, we employed a free myomucosal composite graft from the lower lip to reconstruct small to medium vermilion defects. Our technique is based on a simple and reproducible surgical approach that facilitates natural volume rearrangement of tissues. Moreover, this method enables precise inset and tension-free repair, prevents lip tightening, and offers excellent aesthetic outcomes with no vertical scarring and appropriate color matching with surrounding tissues.

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The internal mammary artery perforator flap in pharyngoesophageal, cervical tracheal, and cutaneous neck reconstruction

Daniel Sharbel, Chen Lin, Michael C. Topf, Kyle Mannion

Publication date 04-06-2024


Abstract The internal mammary artery perforator (IMAP) flap is an evolution of the deltopectoral flap that is harvested based upon a single perforator from the internal mammary artery. Its favorable characteristics include pliability as a fasciocutaneous flap, ease of harvest, and minimal donor site morbidity. In this paper, we report our harvest technique and the versatility of the IMAP flap for pharyngoesophageal, cervical tracheal, and cutaneous neck defects. We seek to highlight the IMAP as a useful regional reconstructive option in both the primary and salvage reconstructive setting. As such, this flap is an important option in the head and neck reconstructive surgeons armamentarium.

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Ethanol embolotherapy of mandibular arteriovenous malformation‐induced acute oral hemorrhage after tooth extraction

Yuchen Shen, Deming Wang, Lixin Su, Xindong Fan, Xitao Yang

Publication date 31-05-2024


Abstract Background Mandibular arteriovenous malformation (AVM) is rare. Our work aims to introduce the ethanol embolization of a patient suffering from acute oral hemorrhage induced by mandibular AVM.
MethodsA 35-year-old woman without coagulopathy underwent tooth extraction, and the acute oral bleeding occurred intraoperatively. Imaging examinations indicated the enhancement of vascular mass with bone destruction inside the mandible. Angiography finally confirmed the high blood flow nature and the diagnosis of AVM.
Results During the interventional procedure, the coils were first applied into the dilated outflowing vein to slow down the blood flow rate of mandibular AVM. Absolute ethanol was injected in a multi-bolus modality to destroy the nidus of AVM. Her mandibular lesion had been stable in the 12-month re-examined angiography, no further bleeding occurred during the period.
Conclusions Ethanol embolotherapy was a less invasive, more precise, and quick-action approach managing AVM of the jaw and related emergency medicine.

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The impact of pretreatment symptom burden on long‐term quality of life following head and neck radiation: A prospective longitudinal study

Colton Ladbury, Taylor Wilde, Arya Amini, Yi Xiao, Ellie Maghami, Erminia Massarelli, Nayana Vora, Virginia Sun, Sagus Sampath

Publication date 30-05-2024


Abstract Background This study characterized the impact of baseline symptom burden on long-term quality-of-life in patients receiving head and neck radiation therapy (RT).
Methods The Vanderbilt Head and Neck Symptom Survey was collected prior to head and neck RT and at follow-up visits. Responses were divided into symptom clusters of toxicities and scored from 0 (asymptomatic) to 10 (severe). Patients with responses at baseline and 1-year or 2-year follow-up were stratified by scores ≤1 or >1 and compared using the Mann–Whitney U-test.
Results At 1-year follow-up (n = 75), patients with higher baseline scores had greater symptom burden for every cluster except in taste/smell. At 2-year follow-up (n = 47), patients with higher baseline scores had greater symptom burden for every cluster except in nutrition, dry mouth, trismus, neck tightness, and hearing.
Conclusion The Vanderbilt Head and Neck Symptom Survey demonstrated a relationship between baseline symptom burden and long-term quality-of-life and might be useful as a screening tool.

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Clinical performance of a prefabricated immunofluorescence assay for nasopharyngeal cancer screening

Vanessa Hui En Chen, Lizhen Ong, Wei Keat Teo, Chor Hiang Siow, Han Lee Goh, Charmaine Tan, Wei Sian Lim, Donovan Eu, Ian S. Y. Cheong, Soh Ha Chan, Kwok Seng Loh, Joshua K. Tay

Publication date 30-05-2024


Abstract Background Epstein–Barr virus (EBV) IgA serology for viral capsid antigen (VCA) and early antigen (EA) aids early detection of nasopharyngeal cancer (NPC), resulting in improved survival. We evaluated the diagnostic performance of a prefabricated immunofluorescent assay (IFA) for NPC screening in high-risk individuals.
Methods Sera from 96 biopsy-proven patients with NPC diagnosed at the outpatient clinic and 96 healthy family members were tested for EBV-VCA IgA and EBV-EA IgA using the prefabricated IFA from EUROIMMUN (EI) and the traditional immunofluorescence method.
Results The AUC of EI EBV-VCA IgA and EBV-EA IgA was 0.907 (95% confidence interval CI: 0.894–0.965) and 0.898 (95% CI: 0.848–0.947), respectively. Combined testing with the prefabricated assay at a threshold of VCA ≥1:320 or EA ≥1:10 showed 92.7% sensitivity and 81.2% specificity. Overall, the traditional EBV-EA IgA assay demonstrated the best accuracy (sensitivity 91.7% and specificity 96.9%) at a threshold of ≥1:5.
Conclusion While the traditional IFA method was more accurate, the prefabricated IFA test kit can be a useful tool for NPC screening in high-risk populations.

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A comparative study of transcervical, endoscope‐assisted transcervical, and endoscope‐assisted transoral resection of retrostyloid space schwannomas

Diekuo Zhang, Helei Yan, Huihong Chen, Donghai Huang, Xingwei Wang, Weihong Jiang, Xin Zhang, Shanhong Lu, Yong Liu

Publication date 29-05-2024


Abstract Background The aim of this retrospective study was to compare the efficacy of transcervical (TC), endoscope-assisted transoral (TO), and endoscope-assisted TC for resection of retrostyloid space schwannomas.
Methods The study included patients who underwent complete resection of schwannomas by only one surgical approach. The data we collected included tumor size, estimated blood loss, postoperative complications, and so on. Statistical analysis was performed using one-way analysis of variance and Fishers exact test.
Results The study collected 85 patients with tumors mostly located at the oropharyngeal level who were followed up 6 months at least. The results showed that endoscope-assisted TO had certain advantages over others. Additionally, the endoscope-assisted TO set the lowest incidence of neurological complications.
Conclusion Our findings demonstrate that for team with rich experience in the skull base surgery, endoscope-assisted TO is a superior option compared to the other two groups for resection of retrostyloid space schwannomas, with the better preservation of neurological function.

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Prognostic factors of tongue cancer in children and adolescents: A SEER population‐based study

Zhihua Jiang, Xianming Yao, Yi Lou, Shaoguang Feng

Publication date 25-05-2024


Abstract Purpose This study aims to analyze the clinicopathological characteristics and survival outcomes of tongue cancer in the pediatric population, a topic with limited existing data, using a population-based cohort.
Methods Pediatric patients diagnosed with tongue cancer from 1975 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were assessed using Kaplan–Meier analysis. Univariate survival analysis was conducted with the log-rank test, while multivariate analysis involved Cox proportional-hazards regression to identify factors influencing overall survival (OS). A predictive nomogram was developed based on Cox regression findings.
Results In total, 97 pediatric patients with tongue cancer were identified, with a median age at diagnosis of 15 years (range: 1–19 years). Tumors were classified as squamous cell carcinoma (45.4%), rhabdomyosarcoma (RMS) (13.4%), and others (41.2%). Of the patients, squamous cell carcinoma was more common in older children, whereas rhabdomyosarcoma was more common in younger children. The Cox proportional hazard regression revealed that histology and surgery were significant independent predictors of overall survival. The chance of death increased with no surgery. Moreover, patients with squamous cell carcinoma or rhabdomyosarcoma have a poorer survival percentage than patients with other subtypes.
Conclusions Tongue cancer in children is rare and associated with poor survival outcomes. This study highlights the significance of tumor histology and surgical intervention in determining overall survival, offering valuable insights for clinical decision-making in pediatric tongue cancer.

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Effect of time‐of‐day nivolumab and stereotactic body radiotherapy in metastatic head and neck squamous cell carcinoma: A secondary analysis of a prospective randomized trial

James R. Janopaul‐Naylor, Lillian Boe, Yao Yu, Eric J. Sherman, David G. Pfister, Nancy Y. Lee, Sean McBride

Publication date 24-05-2024


Abstract Background Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies.
Methods Secondary analysis of prospective, phase II trial of metastatic HNSCC randomized to nivolumab+/−SBRT. Used cutoffs of 1100 and 1630. Timing classified by first infusion or majority of SBRT (e.g., PM SBRT defined by two or three fractions after 1630).
Results Of 62 patients, there was no significant difference in median PFS between AM nivolumab (n = 7, 175 days), PM nivolumab (n = 21, 58 days), or Mid-Day nivolumab (n = 34, 67 days; p = 0.8). There was no significant difference in median PFS with AM SBRT (n = 4, 78 days), PM SBRT (n = 13, 111 days), or Mid-Day SBRT (n = 15, 63 days; p = 0.8). There was no significant difference in Grade 3–4 toxicity or ORR. Sensitivity analyses with other timepoints were negative.
Conclusions Further work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study.

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Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1–T2 HPV Negative oropharyngeal squamous cell carcinoma

Francisco Laxague, Naif Fnais, Hee Young Son, Faisal Alzahrani, Joe S. Mymryk, John W. Barrett, Keng Yow Tay, Andrew Leung, Julie Theurer, Anthony C. Nichols, David A. Palma

Publication date 23-05-2024


Abstract Background Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC.
Methods For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist.
We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan–Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test.
Results Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively).
Conclusion Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

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Skull base surgery for malignant tumors: The 2nd international collaborative study (1995–2015)

Jatin P. Shah, Helena Levyn, Cristina Valero, Dauren Adilbay, Alana Eagan, Junting Zheng, Mithat Gonen, Marc Cohen, Snehal Patel, Ian Ganly, Prathamesh Pai, Paolo Castelnuovo, Fang Ju Gao, Cesare Piazza, Piero Nicolai, Ben Panizza, James Bowman, Catherine Barnett, Luiz P. Kowalski, Ronaldo Toledo, Dan M. Fliss, John DeAlmeida, Ian Witterick, Philippe Herman, Walter Fontanella, Gregorio Sanchez Aniceto, Sefik Hosal, Serdar Ozer, Subramania Iyer, Richard Harvey, C. Rene Leemans, Jan‐Jaap Hendrickx, Marcelo Figari, Luis Boccalatte, Ken Ichi Nibu, Peter Clarke, Catherine Rennie, Zhu Yi Ming, Claudio Cernea, Sergio Goncalves, Rodney Schlosser, Fernando Dias, Zoukaa Sargi, Shahzada Ahmed, Wojciech Golusinski, Se Heon Kim, Shirley Y. Su, Shaan M. Raza, Franco DeMonte, Ehab Hanna

Publication date 21-05-2024


Abstract Background The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide.
Patients and methodsA total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes.
Results The median age was 56 years (IQR 44–67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor.
Conclusion The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

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Hypoxia‐induced SENP3 promotes chemosensitivity and mitochondrial fission via deSUMOylation of Drp1

Yuanyuan Mao, Keyue Liu, Yaocheng Yang, Yiran Liang, ZhaoJian Gong, Kun Wu

Publication date 21-05-2024


Abstract Objective The study aimed to investigate the effect of the SUMOylation status of Drp1 on mitochondrial fission in CDDP-treated HNSCC cells cultured under hypoxic conditions.
Materials and methods The effect of hypoxia on the chemosensitivity of HNCC cells was evaluated by flow cytometry and CCK-8 assays. The biological function of SUMO-specific peptidase 3 (SENP3) was evaluated by loss-of-function assays both in vitro and in vivo. SENP3-regulated deSUMOylation of Drp1 were performed with co-IP assays.
ResultsSENP3 expression correlated with chemosensitivity in clinical HNSCC samples subjected to hypoxic conditions. Hypoxia-induced ROS increased HIF-1α/SENP3 expression and mitochondrial fission in CDDP-treated HNSCC cells, and these effects were reversed by NAC treatment. SENP3 knockdown reversed hypoxia-induced mitochondrial fission and inhibited HNSCC cell apoptosis, which decreased CDDP sensitivity. Furthermore, hypoxia-induced SENP3 deconjugated SUMO2 from Drp1.
Conclusion Our findings revealed that hypoxia-induced SENP3 facilitates CDDP sensitivity and mitochondrial fission via deSUMOylation of Drp1.

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Outcomes of internal mammary artery perforator flap in head and neck reconstruction: A systematic review

Srivatsa Surya Vasudevan, Brianna Rogers, Dauren Adilbay, Lindsay Olinde, John Pang, Cherie‐Ann O. Nathan, Ameya A. Asarkar

Publication date 20-05-2024


Abstract This study aims to evaluate the functional and prognostic outcomes associated with the internal mammary artery perforator (IMAP) flap in various head and neck defect repairs, given the current lack of clarity on its effectiveness.
We performed a systematic review of various databases: Pub Med, Embase, Scopus, Web of Science, and Science Direct using keywords such as “Internal mammary artery perforator flap” and “IMAP.” Screening and data extractions were performed by two individual reviewers. Articles were considered eligible if they included sufficient information on IMAP flap features, their applications in the head and neck, and outcomes. From 264 articles analyzed, 24 studies were included for qualitative analysis. Out of which, 125 patients who received internal mammary artery perforator flaps were included. Most of the patients, 103 (88%), received pedicled IMAP flaps, and 22 (12%) received IMAP free flaps. The second internal mammary artery (IMA) was favored as the single perforator (81.5%), with the combination of the first and second IMA being the primary choice for dual perforators (92.5%). IMAP flaps were predominantly single perforator flaps (65%), with 35% being dual perforator flaps. Among various applications, IMAP flaps are commonly employed in the reconstruction of neck defects (25.5%), pharyngocutaneous fistula repair (20.8%), and burn scar contracture restoration (8%). Only seven (5.6%) patients had flap complications, including venous congestion (1.6%), partial necrosis (1.6%), complete necrosis (1.6%), and incision dehiscence (0.8%). Donor sites were predominantly closed by the primary closure (92%). 3.2% of donor sites had minor complications. The average follow-up was 12.6 (IQR: 6–18) months. This systematic review highlights the effectiveness and safety of IMAP flaps in head and neck reconstruction, with positive outcomes and minimal complications.

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Analysis of trends in radiofrequency ablation in a tertiary care center practice

Zoë Fullerton, Santino S. Butler, Julia Noel

Publication date 20-05-2024


Abstract Background Radiofrequency ablation (RFA) for thyroid nodules has recently been introduced into the United States healthcare system landscape. Little is known about the process of incorporating this procedure into existing clinical practice.
MethodsA retrospective chart review of a single institution was conducted to examine referral patterns and decision-making after the introduction of RFA into an endocrine surgery-focused practice. Patient demographics and thyroid-specific data were recorded. Two reviewers abstracted and coded reasons for the noncompletion of RFA. Two-sample t tests were used to compare groups; linear regression was used to assess trends and practice patterns.
Results Chart review identified 451 patients referred for consideration of RFA from January 2020 to December 2022. Only 255 (56.5%) went on to receive the treatment. There was no significant difference in nodule volume between treated and nontreated groups (18.5 vs. 14.9 cm3, p = 0.07). Concern for malignancy on genetic testing, size (too large/too small), recommendation for Ethanol ablation, and multinodular disease without target nodules were the most common reasons for physician deferral. Of patients who declined to proceed, 46% opted to undergo surgical excision. Linear regression showed that referral numbers significantly increased with time; however, the proportion of patients receiving treatment decreased yearly, primarily because of higher rates of physician deferral.
Conclusions This study reflects the complex decision-making in offering minimally invasive thyroid nodule ablation. Despite a greater number of referrals over time, physician criteria became increasingly selective. Optimal candidacy in RFA is an evolving determination requiring patient and physician input to guide ideal practice patterns.

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Trends of female authorship in head and neck surgery publications over the last decade

Tatiana Ferraro, Jamie Cole, Sean M. Lee, Alisha R. Pershad, Esther Lee, Hannah Hildebrand, Chloe Harrington, Nicole A. Derdzakyan, Beck O. Gold, Neelima Tummala, Punam Thakkar

Publication date 16-05-2024


Abstract Background While other otolaryngology subspecialties have established female authorship trends, there is no comprehensive study within head and neck surgery (HNS).
Methods Five researchers recorded the gender identity of first and senior authors from HNS subspecialty papers (head and neck oncology, endocrine surgery, salivary gland pathology, and microsurgery) derived from 10 journals in otolaryngology and oncology in the years 2013, 2016, 2019, and 2022.
Results From 3457 articles, 6901 unique author identities were analyzed. Female authors represented 32% (N = 1103) of first authors and 20% (N = 690) of senior authors. Female authors were less likely to publish in microvascular and reconstructive surgery. Senior female authors were more likely to publish in higher impact journals than male senior authors, and first female authors had an increased likelihood of funding compared to their male counterparts.
Conclusions While female authors remain underrepresented in certain literature, we illustrate promising trends in productivity, funding allocation, and impact.

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Bioinformatics approach combined with experimental verification reveals OAS3 gene implicated in paclitaxel resistance in head and neck cancer

Hasan Onur Caglar, Abdulmelik Aytatli, Neslisah Barlak, Elanur Aydin Karatas, Arzu Tatar, Abdulkadir Sahin, Omer Faruk Karatas

Publication date 16-05-2024


Abstract Background This study aimed to identify a candidate gene associated with paclitaxel (PTX) resistance and to evaluate functionally its biological role in the PTX-resistant head and neck squamous cell carcinoma (HNSCC) cell lines and clinical specimens.
Methods Microarray data series containing samples of different types of cancers resistant to PTX were analyzed and then a candidate gene associated with PTX resistance was identified using various bioinformatics tools. After the suppression of the target gene expression, changes in cell viability and colony-forming ability were evaluated in PTX-resistant Fa Du and SCC-9 cell lines.
Results Bioinformatics analyses of upregulated genes in PTX-resistant cancer cells indicated that OAS3 was associated with PTX resistance. The downregulation of OAS3 expression significantly reduced the viability and colony-forming capacity of PTX-resistant SCC-9 cells by inducing apoptosis and cell cycle arrest at G0/G1 phase.
Conclusions The therapeutic targeting of OAS3 may resensitize PTX-resistant HNSCC cells with high OAS3 expression to PTX treatment.

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Oral cancer incidence rate is associated with access to dental care: City and statewide analyses

Henrique Ochoa Scussiatto, Seunghee Kim, Marynia A. Kolak, Cheryl C. Nocon, Jayant M. Pinto, Mihir K. Bhayani

Publication date 16-05-2024


Abstract Introduction Access to dental care may affect diagnosis of oral squamous cell carcinoma (OSCC). We tested whether the incidence rate of OSCC is higher in regions with less dental care access in the city of Chicago and state of Illinois.
Study Design Ecological cohort.
Setting Population, outpatients, and inpatients.
Methods We extracted 5-year averages of the state-wide county-level and city-level OSCC incidence rates from 2015 to 2019 from the Illinois Department of Public Health. Dental care access information was also collected for each county for the same period, as well as the percentage of people that had ≥1 visit to a dentist in the previous year in Chicago. Multivariate Poisson regression was used to investigate the relationship between county-level access to dental care (and city-level dentist visits) and OSCC incidence rate, controlling for confounders, with additional flexible semiparametric models for confirmatory sensitivity analysis.
Results In Illinois, higher 5-year incidence rate of OSCC was significantly associated with low access to dental care by county (IRR = 0.96, 95% CI 0.91, 0.98). Southern/southwestern counties had higher incidence rates of OSCC (15.5%–28.4%) and the lowest rates of dental care access (47.5%–69.2%) compared to northern counties (10.3%–15% and 55.4%–80.6%, respectively). In Chicago, people with more dentist visits had a reduced chance of being diagnosed with OSCC (IRR = 0.97, 95% CI 0.91, 0.99), consistent with state-wide analyses.
ConclusionOSCC incidence rate is closely associated with poor local dental healthcare access in a major state and urban city. Increasing dental access could improve cancer outcomes via improved oral health and earlier detection.

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Alberta reconstructive technique (ART): An innovative approach using digital surgical design and simulation in advanced jaw reconstruction with occlusion‐based prefabricated vascularized fibular flaps and primary osseointegrated implant installation

"Suresh Nayar, Heather Logan, Johan Wolfaardt, Martin Osswald, Daniel OConnell, Andrew Grosvenor, Hadi Seikaly"

Publication date 14-05-2024


Abstract The Alberta reconstructive technique (ART) is an innovative surgical procedure performed on patients undergoing primary jaw resection and reconstruction. The ART procedure was developed in collaboration with the Institute for Reconstructive Sciences in Medicine and the Division of Otolaryngology—Head and Neck Surgery, University of Alberta.

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Immediate dental rehabilitation in fibula free flaps for malignancy: Is it feasible?

Jonathan Jelmini, Fayette C. Williams, Michael Winstead, Daniel A. Hammer, Roderick Y. Kim

Publication date 10-05-2024


Abstract Background Fibula free flap reconstruction has revolutionized maxillofacial reconstruction. While immediate dental rehabilitation with dental implants and teeth has shown benefits, it remains uncommon, especially for patients with malignancy.
MethodsA retrospective cohort study at a single institution explored immediate dental rehabilitation in fibula flaps for patients with malignant disease. Thirteen patients with malignancies that underwent immediate fibula free flap reconstruction with dental implants and dental prosthesis were included with a minimum of 3-month follow-up.
Results Forty eight implants replaced 90 teeth in 13 patients. All implants were integrated at 3 months, with an overall success rate of 87.5%. Two patients experienced delayed (>3 months postoperatively) implant loss due to osteoradionecrosis and infection. Peri-mucositis occurred in three patients which resolved with treatment. Skin paddles were used in 11 patients and radiation therapy was not delayed for any patient.
Conclusion With proper patient selection, diagnosis of malignancy and the need for osteocutaneous flap reconstruction does not exclude the ability to place immediate implants and deliver an immediate dental prosthesis in head and neck reconstruction.

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Salvage surgery for recurrent or residual hypopharyngeal squamous cell carcinoma: A systematic review

Peter V. Cooke, Michael P. Wu, Vinay K. Rathi, Sida Chen, Catharine Kappauf, Scott A. Roof, Derrick T. Lin, Daniel G. Deschler

Publication date 08-05-2024


Abstract Background This systematic review aggregates the data of studies that include site-specific analyses of patients undergoing salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma.
Methods The primary outcomes are disease-free, disease-specific, and overall survival (DFS, DSS, and OS, respectively). Secondary outcomes include complications and postoperative feeding requirements.
Results Fifteen studies met the inclusion criteria with a total of 442 patients. Two-year DFS is reported from 30.0 to 50.0% and 5-year DFS ranges from 15.0 to 57.1%. Five-year DSS ranges from 28.0 to 57.1%. Two-year OS ranges from 38.8 to 52.0% and 5-year OS ranges from 15.5 to 57.1%. Complications include pharyngocutaneous fistula (0.0–71.4%), carotid artery rupture (2.9–13.3%), and stomal stenosis (4.2–20.0%). Complete oral feeding achieved following surgery ranges from 61.9 to 100.0%, while complete gastrostomy tube dependence ranges from 0.0 to 28.6%.
Conclusions Salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma has a relatively high complication rate and should be offered to patients with the understanding of a guarded prognosis.

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Diagnostic value of 18F‐FDG PET/CT versus diffusion‐weighted MRI in detection of residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal squamous cell carcinoma: A prospective study

Soung Yung Kim, David Crook, Johannes Rosskopf, Jung‐Hyun Lee

Publication date 07-05-2024


Abstract Background Despite advances in treatment, residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal squamous cell carcinoma (SCC) remain a challenge in clinical management and require accurate and timely detection for optimal salvage therapy. This study aimed to compare the diagnostic value of Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal SCC.
MethodsA prospective study was conducted on 30 patients who presented with new symptoms after definitive (chemo) radiotherapy for laryngeal (n = 21) and hypopharyngeal (n = 9) carcinoma. Both 18F-FDG PET/CT and DW-MRI were performed and histopathologic analysis served as the standard of reference.
Results Histopathology showed 20 patients as positive and 10 as negative for tumors. 18F-FDG PET/CT detected all tumors correctly but was falsely positive in one case. DW-MRI detected tumors in 18 out of 20 positive patients and correctly excluded tumors in all negative patients. The sensitivity and specificity of 18F-FDG PET/CT were 100% and 90%, respectively, while the values for DW-MRI were 90% and 100%, respectively.
Conclusions The study concludes that 18F-FDG PET/CT is slightly superior to DW-MRI in detecting residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal SCC. The combined use of 18F-FDG PET/CT and DW-MRI can potentially improve specificity in therapy response evaluation.

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Exercise adherence for patients with trismus after head and neck cancer treatment

Emma Charters, Jamie Loy, Ashleigh R. Sharman, Kai Cheng, Masako Dunn, Jonathan Clark

Publication date 06-05-2024


Abstract Background Head and neck cancer treatment often leads to trismus, a condition characterized by limited mouth opening. Exercise-based therapy is the most common intervention but there are no clear guidelines as to the optimal exercise regimen. Restorabite™ is a portable and force-regulated trismus device designed to enhance exercise adherence. This study explores the adherence to exercises using Restorabite™ in head and neck cancer patients with trismus and identifies facilitators and barriers to exercise therapy.
Materials and methods Mixed-methods, prospective cohort study undertaken at a quaternary oncology hospital, in Sydney Australia involving participants diagnosed with head and neck cancer diagnosed with trismus (maximal incisal opening under 35 mm). Patients underwent a 10-week individualized trismus program using Restorabite™ with weekly speech pathology reviews. Exercise adherence was tracked through categorized descriptors. Data were collected prospectively at baseline, during 10 weeks of therapy with Restorabite™, and at 6- and 12-month post-trismus exercise. Participants described facilitators of trismus therapy, and barriers to completing the prescribed exercises. Clinical documentation of these responses was then analyzed using content analysis.
Results One-hundred and thirty-five participants were recruited. During the intervention 69% (n = 93) exercised as recommended, 24% (n = 32) exercised less, and 7% (n = 10) exercised more than recommended. At 6 months post-intervention, 55.5% (n = 75) exercised as recommended, 38.5% (n = 52) exercised less, and 4% (n = 6) exercised more. At 12 months, 36% (n = 49) exercised as recommended, 48% (n = 62) exercised less, and 11% (n = 15) exercised more. MIO increased from a mean of 18.6 mm at baseline, to 30.1 mm at the end of the 10-week intervention. This was maintained at 6 and 12 months (31.7 and 32.1 mm, respectively). Adherence to the exercise program was associated with greater improvement in maximum interincisal opening (p < 0.001). Facilitators of adherence included intrinsic motivation, device portability, perceived functional change, and external support tools. Barriers included cancer treatment toxicities, competing priorities, and health challenges. Positive outcomes included functional improvements, while negative outcomes included increased pain.
Conclusions Seventy-six percent of patients prescribed Restorabite™ performed trismus exercises at or more than the recommended frequency. Facilitators and barriers identified provide insights into factors influencing adherence. Future research should involve comparative studies that compare the adherence and effectiveness of different exercise programs.

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How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck

Alexis Miller, Vickie Wang, Victor Jegede, Fabian Necker, Joseph Curry, Fred M. Baik, Avanti Verma, F. Christopher Holsinger, Madalina Tuluc, Mobeen Rahman, James S. Lewis Jr, Eben Rosenthal, Michael C. Topf

Publication date 04-05-2024


Abstract Background Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy.
Methods Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave).
ResultsA total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins.
Conclusions Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

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Evaluation of aesthetic outcomes of mandibular reconstruction using artificial intelligence

Takeaki Hidaka, Shimpei Miyamoto, Kiichi Furuse, Yutaka Fukunaga, Azusa Oshima, Kazuto Matsuura, Takuya Higashino

Publication date 03-05-2024


Abstract Background Although vascularized bone graft (VBG) transfer is the current standard for mandibular reconstruction, reconstruction with a mandibular reconstruction plate (MRP) and with a soft-tissue flap (STF) alone remain crucial options for patients with poor general conditions. However, objective aesthetic outcome evaluations for these methods are limited.
Methods In a retrospective analysis of 65 patients (VBG, 33; MRP, 19; and STF, 13), mandibular asymmetry value was calculated for each patients photograph using facial recognition AI, with a higher value indicating worse asymmetry.
Results The MRP group had a value comparable to the VBG group regardless of mandibular defect types. The STF group had a significantly higher value than the VBG group.
Conclusions Regarding cosmesis, STF was inferior to VBG, whereas MRP was comparable to VBG, even for anterior defects for which rigid reconstruction is mandatory. However, MRPs risks of plate-related complications limit its use to cases where VBG is contraindicated or with poor prognosis.
Level of Evidence4.

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Assessing survival outcomes of patients with oral tongue squamous cell carcinoma: Focus on age, sex, and stage

Saagar Pamulapati, Marin Abousaud, Yixuan Li, Asari Ekpenyong, Soumon Rudra, Jill S. Remick, James E. Bates, William A. Stokes, Mark W. McDonald, Nicole C. Schmitt, Mark W. El‐Deiry, Mihir R. Patel, Conor E. Steuer, Jeffrey M. Switchenko, Dong M. Shin, Yong Teng, Anthea Hammond, Nabil F. Saba

Publication date 02-05-2024


Abstract Background The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma.
Methods This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan–Meier method.
ResultsA total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%–84.0%) in younger patients versus 67.5% (95% CI: 66.7%–68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2–NA) versus 129.8 (95% CI: 125.4–138.7, p-value <0.0001) in males.
Conclusions Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma.

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Follow‐up for human papillomavirus‐related oropharynx cancer concentrated on unequal symptom change (FOCUS): Prospective patient‐reported outcome collection

Donna M. Edwards, Laila A. Gharzai, Weilin Wang, Charles Mayo, Krithika Suresh, Matthew Schipper, Joseph R. Evans, Kelly Malloy, Steven B. Chinn, Mark Prince, Matthew Spector, Andrew Shuman, Chaz Stucken, Paul L. Swiecicki, Francis Worden, Jennifer Jarema, Caitlin Henderson, Amanda Kovach, Chad Brenner, Jennifer L. Shah, Michelle L. Mierzwa, Keith Casper

Publication date 29-04-2024


Abstract Background Post-treatment surveillance recommendations for oropharyngeal cancer do not vary with p16 status despite the differences in outcomes. The optimal algorithm personalizing follow-up for these patients remains undefined. Here, we evaluate the feasibility and utility of incorporating electronic patient-reported outcomes (ePROs) and circulating tumor DNA (ctDNA) into routine surveillance for patients treated for p16+ oropharynx cancer.
MethodsA prospective registry was developed in which ePROs and ctDNA were incorporated into routine surveillance among patients with oropharynx cancer. ePROs were emailed monthly for 1 year and blood HPV ctDNA testing was performed every 3–6 months. The primary objective was to assess patient compliance with ePRO-based surveillance with adequate compliance defined as ≥85% of patients completing monthly ePROs. Sensitivity, specificity, and positive/negative predictive values to detect recurrence were calculated for ePROs, HPV ctDNA, or the combination.
Results Of 122 patients who initially expressed interest, 76 completed the electronic consent process and 44/76 (58%) were compliant with monthly surveys over 1 year; thus adequate compliance was not achieved. Technical difficulties associated with ePRO receipt through email largely limited participation. Provider feedback was significantly associated with heightened ePRO compliance. One hundred and six patients had ctDNA testing with a mean number of three tests per patient. Sensitivity to detect recurrence was 75% for the combination of ePROs and ctDNA.
Conclusion Despite lower than anticipated compliance with ePROs, our findings show promise for incorporation of HPV ctDNA into surveillance paradigms for HPV-related oropharynx cancer with suggestions of methods to optimize ePRO formats for personalized surveillance.

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Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD‐L1 and PD‐L2

Ryosuke Sato, Hiroki Komatsuda, Takahiro Inoue, Risa Wakisaka, Michihisa Kono, Hidekiyo Yamaki, Kenzo Ohara, Takumi Kumai, Kan Kishibe, Tatsuya Hayashi, Miki Takahara

Publication date 26-04-2024


Abstract Background Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established.
Methods The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab.
Results The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated.
Conclusions Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

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Effects of tislelizumab on health‐related quality of life in patients with recurrent or metastatic nasopharyngeal cancer

Yunpeng Yang, Jianji Pan, Nianyong Chen, Ye Guo, Xiaoming Huang, Yanjie Wu, Shiangjiin Leaw, Fan Bai, Yu Wang, Na Zhao, Boxiong Tang, Gisoo Barnes

Publication date 26-04-2024


Abstract Background This study evaluated health-related quality of life (HRQoL) in the RATIONALE-309 (NCT03924986) intent-to-treat (ITT) population and in a subgroup of patients with liver metastases.
Methods Patients were randomized 1:1 to tislelizumab + chemotherapy or placebo + chemotherapy. As the secondary endpoint, HRQoL was evaluated using seven selected scores from the EORTC QLQ-C30 and QLQ Head and Neck Cancer module (QLQ-H&N35).
Results Of 263 randomized patients in the ITT population (tislelizumab + chemotherapy n = 131, placebo + chemotherapy n = 132), 43% had liver metastases (tislelizumab + chemotherapy n = 56; placebo + chemotherapy n = 57). No differences in change in selected scores on the QLQ-C30 from baseline to cycle 4 or cycle 8 were observed for the ITT or liver metastases subgroup. No differences in selected QLQ-H&N35 scores were observed between the arms from baseline to cycle 4. In the ITT population and the liver metastases subgroup, a greater reduction from baseline to cycle 8 was observed in the tislelizumab + chemotherapy arm than the placebo + chemotherapy arm in QLQ-H&N35 pain score. At cycle 8 in the liver metastases subgroup, the tislelizumab + chemotherapy arm experienced greater improvement in the QLQ-H&N35 senses problems score than the placebo + chemotherapy arm. Differences in time to deterioration between arms were not observed.
Conclusions The current findings, along with improved survival and favorable safety, suggests that tislelizumab + chemotherapy represents a potential first-line treatment for recurrent or metastatic nasopharyngeal cancer.

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Causes and impact of delays during the COVID‐19 pandemic on head and neck cancer diagnosis

"Maru Gete, Shao Hui Huang, Jolie Ringash, Jonathan Irish, Jie Su, Yashi Ballal, John N. Waldron, Ian Witterick, John de Almeida, Ali Hosni, Andrew J. Hope, Eric Monteiro, John Cho, Brian OSullivan, John Kim, Scott Bratman, David P. Goldstein, Andrew McPartlin, Jillian Tsai, Li Tong, Wei Xu, Ezra Hahn"

Publication date 25-04-2024


Abstract Background The causes for delays during the COVID19 pandemic and their impact on head and neck cancer (HNC) diagnosis and staging are not well described.
Methods Two cohorts were defined a priori for review and analysis—a Pre-Pandemic cohort (June 1 to December 31, 2019) and a Pandemic cohort (June 1 to December 31, 2020). Delays were categorized as COVID-19 related or not, and as clinician, patient, or policy related.
ResultsA total of 638 HNC patients were identified including 327 in the Pre-Pandemic Cohort and 311 in the Pandemic Cohort. Patients in the Pandemic cohort had more N2-N3 category (41% vs. 33%, p = 0.03), T3-T4 category (63% vs. 50%, p = 0.002), and stage III-IV (71% vs. 58%, p < 0.001) disease. Several intervals in the diagnosis to treatment pathway were significantly longer in the pandemic cohort as compared to the Pre-Pandemic cohort. Among the pandemic cohort, 146 (47%) experienced a delay, with 112 related to the COVID-19 pandemic; 80 (71%) were clinician related, 15 (13%) were patient related, and 17 (15%) were policy related.
Conclusions Patients in the Pandemic cohort had higher stage disease at diagnosis and longer intervals along the diagnostic pathway, with COVID-19 related clinician factors being the most common cause of delay.

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Masseter muscle thickness is predictive of cancer cachexia in patients with head and neck cancer

Julián Balanta‐Melo, Alexander J. Jones, Leah J. Novinger, Michael G. Moore, Andrea Bonetto

Publication date 25-04-2024


Abstract Background Cancer cachexia is prevalent in head and neck cancer patients. The L3 skeletal muscle index (SMI) is often used to assess sarcopenia and cachexia but is infrequently able to be measured in this population. Masseter muscle thickness (MT) may serve as an alternative predictor of cachexia.
MethodsSMI and MT were calculated from 20 trauma (CTRL) and 40 cachectic (CA-CX) and non-cachectic (CA-NCX) head and neck cancer patients. Area Under the Curve of the Receiver Operating Characteristics (AUC-ROC) analysis was performed for SMI and MT.
Results Both SMI and MT were significantly decreased in CA-CX patients (vs. CA-NCX mean difference −19.5 cm2/m2 and −2.06 mm, respectively) and significant predictors of CA-CX (AUC = 0.985 and 0.805, respectively). When analyzed by sex, the same findings were observed for MT in males and trended toward significance in females.
Conclusions Compared with SMI, MT is a good alternative prognostic biomarker to determine CA-CX status in HNC patients.

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Evaluating the impact of the degree of extranodal extension on outcomes in locally advanced oral cavity cancer

Anirudh Yalamanchali, Christopher Griffith, Chandana A. Reddy, Shlomo A. Koyfman, Neil M. Woody, Shauna R. Campbell, Natalie Silver, Joseph Scharpf, Robert R. Lorenz, Brandon Prendes, Jamie A. Ku, Eric Lamarre, Jessica L. Geiger

Publication date 25-04-2024


Abstract Background Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC).
Methods From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent.
Multivariable Cox regression was used to relate patient/treatment characteristics with disease-free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable.
ResultsA total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72–1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70–1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87–1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83–1.11, p = 0.58).
Conclusion No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC.

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Primary fit tracheoesophageal puncture in primary versus salvage laryngectomy: Short‐term and long‐term complications and functional outcomes

Emese C. Kanyo, Shannon S. Wu, Chandana A. Reddy, Natalie L. Silver, Eric D. Lamarre, Brian B. Burkey, Brandon L. Prendes, Joseph Scharpf, Robert R. Lorenz, Joann Kmiecik, Jamie A. Ku

Publication date 24-04-2024


Abstract Background Primary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary-fit TEP in the setting of salvage laryngectomy.
MethodsA retrospective, single-center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short-term and long-term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy.
Results In this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes.
Conclusion Primary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.

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Assessing social vulnerabilities of salivary gland cancer care, prognosis, and treatment in the United States

"Govind S. Bindra, David J. Fei‐Zhang, Atharva Desai, John Maddalozzo, Stephanie S. Smith, Urjeet A. Patel, Daniel C. Chelius, Jill N. DSouza, Jeffrey C. Rastatter, M. Boyd Gillespie, Anthony M. Sheyn"

Publication date 23-04-2024


Abstract Background Salivary gland cancers (SGC)-social determinants of health (SDoH) investigations are limited by narrow scopes of SGC-types and SDoH. This Social Vulnerability Index (SVI)-study hypothesized that socioeconomic status (SES) most contributed to SDoH-associated SGC-disparities.
Methods Retrospective cohort of 24 775 SGCs assessed SES, minority-language status (ML), household composition (HH), housing-transportation (HT), and composite-SDoH measured by the SVI via regressions with surveillance and survival length, late-staging presentation, and treatment (surgery, radio-, chemotherapy) receipt.
Results Increasing social vulnerability showed decreases in surveillance/survival; increased odds of advanced-presenting-stage (OR: 1.12, 95% CI: 1.07, 1.17), chemotherapy receipt (OR: 1.13, 95% CI: 1.03, 1.23); decreased odds of primary surgery (0.89, 0.84, 0.94), radiotherapy (0.91, 0.85, 0.97, p = 0.003) for SGCs. Trends were differentially correlated with SES, ML, HH, and HT-vulnerabilities.
Conclusions Through quantifying SDoH-derived SGC-disparities, the SVI can guide targeted initiatives against SDoH that elicit the most detrimental associations for specific sociodemographics.

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Predicting the overall survival and progression‐free survival of nasopharyngeal carcinoma patients based on hemoglobin, albumin, and globulin ratio and classical clinicopathological parameters

Zui Chen, Jie Ling, Sujuan Zhang, Yuhua Feng, Yangchun Xie, Xianling Liu, Tao Hou

Publication date 22-04-2024


Abstract Background Serum biomarkers have a significant impact on the prediction of treatment outcomes in patients diagnosed with nasopharyngeal carcinoma (NPC). The primary aim of this study was to develop and validate a nomogram that incorporates hemoglobin, albumin, and globulin ratio (HAGR) and clinical data to accurately forecast treatment outcomes in patients with NPC.
MethodsA total of 796 patients diagnosed with NPC were included in the study.
Results The results of the multivariate Cox analysis revealed that TNM stage and HAGR were found to be significant independent prognostic factors for OS and PFS. Furthermore, the utilization of the nomogram demonstrated a significant improvement in the evaluation of OS, PFS compared with the eighth TNM staging system. Additionally, the implementation of Kaplan–Meier curves and decision curve analysis curves further confirmed the discriminability and clinical effectiveness of the nomogram.
Conclusions The HAGR, an innovative prognostic factor grounded in the realm of immunonutrition, has emerged as a promising prognostic marker for both OS and PFS in individuals afflicted with NPC.

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Heterogeneous characterization of neutrophilic cells in head and neck cancers

Magdalena Fay, Paul E. Clavijo, Clint T. Allen

Publication date 15-04-2024


Abstract Background Neutrophilic cells are among the most abundant immune populations within the head and neck tumor microenvironment (TME) and harbor multiple mechanisms of immunosuppression. Despite these important features, neutrophilic cells may be underrepresented in contemporary studies that aim to comprehensively characterize the immune landscape of the TME due to discrepancies in tissue processing and analysis techniques. Here, we review the role of pathologically activated neutrophilic cells within the TME and pitfalls of various approaches used to study their frequency and function in clinical samples.
Methods The literature was identified by searching Pub Med for “immune landscape” and “tumor immune microenvironment” in combination with keywords describing solid tumor malignancies. Key publications that assessed the immune composition of solid tumors derived from human specimens were included. The tumor and blood processing methodologies in each study were reviewed in depth and correlated with the reported abundance of neutrophilic cells.
Results Neutrophilic cells do not survive cryopreservation, and many studies fail to identify and study neutrophilic cell populations due to cryopreservation of clinical samples for practical reasons. Additional single-cell transcriptomic studies filter out neutrophilic cells due to low transcriptional counts.
Conclusions This report can help readers critically interpret studies aiming to comprehensively study the immune TME that fail to identify and characterize neutrophilic cells.

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Quality of life after surgical treatments for facial palsy: A systematic review and meta‐analysis

Johannes N. van der Lely, Niek J. Nieuwdorp, Ineke C. A. W. Smits, Floris V. W. J. van Zijl, Eveline M. L. Corten, Marc A. M. Mureau

Publication date 10-04-2024


Abstract Background Facial palsy profoundly affects patients quality of life (QoL). We evaluated the effect of various surgical procedures on QoL using patient-reported outcome measures (PROMs) to provide evidence-based recommendations for improved care.
Methods Embase, Medline, Web of Science, Cochrane, and CINAHL were searched for studies on QoL in patients with facial palsy who had undergone reconstructive surgery with preoperative and postoperative data from validated PROMs. After conducting the quality assessment, data were subtracted from the articles. Meta-analyses of subgroups were performed when study outcomes where compatible.
Results Incorporating 24 studies (522 patients), our systematic review revealed consistent and significant QoL improvements following diverse reconstructive surgical procedures.
Conclusions Our systematic review and meta-analysis showed the positive effects of different reconstructive surgical procedures on QoL of patients with facial palsy. These results support clinicians to better inform patients about their potential outcomes, optimizing informed and shared decision-making and ultimately improving overall QoL in patients with facial palsy.

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p16 overexpression identifies oncogenic high‐risk HPV infection in non‐oropharyngeal squamous cell carcinoma of the head and neck

Anne‐Sophie Becker, Jenny Merkel, Inci Bozkurt, Daniel Fabian Strüder, Claudia Maletzki, Maja Hühns, Annette Helene Zimpfer

Publication date 09-04-2024


Abstract Background Human papillomavirus (HPV) is an increasing risk factor for cancer. HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC. In oral and laryngeal squamous cell carcinoma (OSCC/LSCC), the relevance of p16 immunohistochemistry, alone or in combination with other cell cycle-related proteins, to identify HPV-driven non-OPSCC is less well understood.
Methods We stained for p16, p Rb, cyclin D1, and p53 in 327 HNSCC. In 310 OPSCC, HPV-status was assessed by HPV DNA PCR. In 119 non-OPSCC, RNA in situ hybridization was additionally performed. HPV-status was correlated with staining patterns, p53 and clinical data.
Results The OPSCC showed blockstaining for p16 in 36%, 8% were equivocal. Of these, HPV-testing was performed in 57%, and 53% were positive for HPV DNA. HPV-association correlated with absence of p Rb and cyclin D1 and favorable outcome. In non-OPSCC, 18% showed p16-blockstaining, and 13% showed E6/E7 RNA. Six of seven HPV+ OSCC and 8/8 LSCC lost p Rb and cyclin D1. Compared to HPV-negative counterparts, patients with HPV+ cancers had lower rates of alcohol consumption and keratinizing morphology. HPV-positive OSCC had a longer overall survival (p < 0.05). HPV subtype 16 was the most common.
Conclusions We conclude that HPV-positive non-OPSCC are associated with p16 overexpression and low levels of p Rb and cyclin D1. High expression of p Rb and cyclin D1 indicates HPV-negativity.

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Radioactive iodine therapy improves overall survival outcome in oncocytic carcinoma of the thyroid\xa0by reducing death risks from noncancer causes: A competing risk analysis of 4641 patients

Kun Zhang, Xinyi Wang, Tao Wei, Zhihui Li, Jingqiang Zhu, Ya‐Wen Chen

Publication date 04-04-2024


Abstract Background Oncocytic carcinoma of the thyroid (OCA) is an independent type of thyroid cancer. Radioactive iodine (RAI) therapy was frequently administered to OCA patients, but its contribution to improving survival is indefinite.
Methods4641 OCA patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression and competing risk analysis were applied.
Results Tumor size, SEER stage, primary surgery, and neck dissection were prognostic factors for cancer-specific survival. The results of competing risk analysis demonstrated that age over 55 years dramatically increased non-OCA death risks. Treatments that improve non-OCA survival (including total thyroidectomy, RAI therapy, and systemic therapy) should be recommended in OCA patients older than 55 years of age. Neck lymphadenectomy should not be recommended for OCA, since the metastatic lymph node ratio was low (about 3%).
ConclusionsRAI therapy can improve survival in OCA by reducing noncancer death risks.

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Optimal cut‐off value for identifying objective response in patients with nasopharyngeal carcinoma after induction chemotherapy

Chao Luo, Wenjie Huang, Shuqi Li, Haojiang Li, Guangying Ruan, Gui Fu, Lizhi Liu

Publication date 28-03-2024


Abstract Background We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC).
Methods According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut-off value. Survival rates and differences between groups were compared with Kaplan–Meier curves and log-rank tests.
Results Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut-off value maximized between-group differences according to maximally selected rank statistics. No difference in distant metastasis-free survival between OR and non-response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed.
Conclusions With an optimal cut-off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients.

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Separating distant recurrences from second primaries in head and neck squamous cell carcinomas – A DAHANCA group analysis on paired tumor samples

Julie Kjems, Jacob Kinggaard Lilja‐Fischer, Jeppe Friborg, Trine Tramm, Jens Overgaard

Publication date 25-03-2024


Abstract Background In head and neck squamous cell carcinomas (HNSCC), there is no clinically available method to separate distant metastases (DMs) from SCC secondary primary tumors. The study aimed to assess the genetic relationship in paired tumor samples.
Methods Patients with pairs of solid biopsies from the primary HNSCC and suspected DMs were identified (2007–2017). Targeted next-generation sequencing of 22 genes was applied, including TP53, supplemented with human papillomavirus (HPV) genotyping.
Results Of 55 pairs obtained, 33 were successfully analyzed. Distant biopsies included lung, liver, and bone. A genetic match was found in 23/33 (70%) patients, primarily with identical TP53 mutations or HPV genotypes. In 10/33 patients (30%), the genetic relationship was absent, all with lung involvement. In patients with no lung involvement, 8/8 had a match.
Conclusions One-third of patients with DMs in HNSCC lack a genetic relationship with the primary tumors. The risk of misclassification is most prominent for patients with lung involvement.

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Parental leave and family building experiences among head and neck surgeons in the United States: Career impact and opportunities for improvement

Caitlin McMullen, Alexandra Kejner, Elizabeth Nicolli, Marianne Abouyared, Orly Coblens, Katie Fedder, Punam Thakkar, Rusha Patel

Publication date 21-03-2024


Abstract Background The availability of paid parental leave is an important factor for retention and wellness. The experiences of head and neck surgeons with parental leave have never been reported.
MethodsA survey was electronically distributed to head and neck subspecialty surgeons in the United States. Responses were collected and analyzed.
Results Male surgeons had more children and took significantly less parental leave than women. Thirty percent of respondents reported that parental leave negatively impacted compensation, and 14% reported a delay in promotion due to leave, which impacted women more than men. The vast majority reported they are happy or neutral about covering those on leave. Most respondents utilized paid childcare, and approximately one quarter of respondents spending 11%–20% of their income on childcare.
Conclusions This study illuminates the current disparities regarding parental leave-taking within the subspecialty of head and neck surgery in the United States. Women surgeons are more likely to be impacted professionally and financially.

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Rate of occult metastasis in lip squamous cell carcinoma: A systematic review and meta‐analysis

Sagar Kansara, Evrim Oral, Indrani Sarkar, Vlad Sandulache, Rula Mualla, Rohan R. Walvekar, William Ryan, Patrick Ha

Publication date 18-03-2024


Abstract Objectives The rate of occult metastasis in lip cancer is poorly studied. Management of the regional nodal basin in lip cancer is thus controversial. This study sought to understand the true rate of micrometastasis in lip cancer.
Materials and Methods Systematic review and meta-analysis was conducted of English language studies reporting lip cancer sentinel node biopsy results. Studies were obtained from the Pub Med database between the years 2000 and 2023 using the search terms “sentinel node biopsy” and “squamous cell carcinoma.” Random effect and fixed effect meta-analyses were performed.
Results Thirteen studies met inclusion criteria. Low heterogeneity was noted among the studies, as indicated by the I2 inconsistency test (I2 = 0%). The rate of occult metastasis ranged between 0 and 33% (mean 9%). A total of 189 lip sentinel node biopsies had been performed. Of these, 21 revealed occult nodal metastasis (11.1%, 95% CI 7.36%–16.44%). One step, generalized linear mixed modeling revealed the true rate of occult nodal metastasis to be 10% (95% CI (0.0504, 0.1746), p < 0.0001).
Conclusion The rate of occult metastasis in lip cancer approaches the threshold for elective management of the regional nodal basin. Sentinel node biopsy is optimally suited for management of high-risk early T stage lip cancer.

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