Role of TORS as De-Escalation Strategy in HPV-Related Oropharyngeal Cancer, What We Need to Know.

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and opportunities for treatment, particularly regarding de-escalation strategies to reduce treatment morbidity without compromising oncological outcomes. This paper examines the role of Transoral Robotic Surgery (TORS) as a de-escalation strategy in managing HPV-related OPSCC. We conducted a comprehensive literature review from January 2010 to June 2023, focusing on studies exploring TORS outcomes in patients with HPV-positive OPSCC. These findings highlight TORS's potential to reduce the need for adjuvant therapy, thereby minimizing treatment-related side effects while maintaining high rates of oncological control. TORS offers advantages such as precise tumor resection and the ability to obtain accurate pathological staging, which can guide the tailoring of adjuvant treatments. Some clinical trials provide evidence supporting the use of TORS in specific patient populations. The MC1273 trial demonstrated promising outcomes with lower doses of adjuvant radiotherapy (RT) following TORS, showing high locoregional tumor control rates and favorable survival outcomes with minimal side effects. ECOG 3311 evaluated upfront TORS followed by histopathologically directed adjuvant therapy, revealing good oncological and functional outcomes, particularly in intermediate-risk patients. The SIRS trial emphasized the benefits of upfront surgery with neck dissection followed by de-escalated RT in patients with favorable survival and excellent functional outcomes. At the same time, the PATHOS trial examined the impact of risk-adapted adjuvant treatment on functional outcomes and survival. The ongoing ADEPT trial investigates reduced-dose adjuvant RT, and the DART-HPV study aims to compare standard adjuvant chemoradiotherapy (CRT) with a reduced dose of adjuvant RT in HPV-positive OPSCC patients. These trials collectively underscore the potential of TORS in facilitating treatment de-escalation while maintaining favorable oncological and functional outcomes in selected patients with HPV-related OPSCC. The aim of this scoping review is to discuss the challenges of risk stratification, the importance of HPV status determination, and the implications of smoking on treatment outcomes. It also explores the evolving criteria for adjuvant therapy following TORS, focusing on reducing radiation dosage and volume without compromising treatment efficacy. In conclusion, TORS emerges as a viable upfront treatment option for carefully selected patients with HPV-positive OPSCC, offering a pathway toward treatment de-escalation. However, selecting the optimal candidate for TORS-based de-escalation strategies is crucial to fully leverage the benefits of treatment de-intensification.

The Use of Artificial Intelligence in Head and Neck Cancers: A Multidisciplinary Survey.

Artificial intelligence (AI) approaches have been introduced in various disciplines but remain rather unused in head and neck (H&N) cancers. This survey aimed to infer the current applications of and attitudes toward AI in the multidisciplinary care of H&N cancers. From November 2020 to June 2022, a web-based questionnaire examining the relationship between AI usage and professionals' demographics and attitudes was delivered to different professionals involved in H&N cancers through social media and mailing lists. A total of 139 professionals completed the questionnaire. Only 49.7% of the respondents reported having experience with AI. The most frequent AI users were radiologists (66.2%). Significant predictors of AI use were primary specialty (V = 0.455; p < 0.001), academic qualification and age. AI's potential was seen in the improvement of diagnostic accuracy (72%), surgical planning (64.7%), treatment selection (57.6%), risk assessment (50.4%) and the prediction of complications (45.3%). Among participants, 42.7% had significant concerns over AI use, with the most frequent being the 'loss of control' (27.6%) and 'diagnostic errors' (57.0%). This survey reveals limited engagement with AI in multidisciplinary H&N cancer care, highlighting the need for broader implementation and further studies to explore its acceptance and benefits.

A new 3D-printed temporal bone: 'the SAPIENS'-specific anatomical printed-3D-model in education and new surgical simulations.

PURPOSE: Otology and neuro-otology surgeries pose significant challenges due to the intricate and variable anatomy of the temporal bone (TB), requiring extensive training. In the last years 3D-printed temporal bone models for otological dissection are becoming increasingly popular. In this study, we presented a new 3D-printed temporal bone model named 'SAPIENS', tailored for educational and surgical simulation purposes. METHODS: The 'SAPIENS' model was a collaborative effort involving a multidisciplinary team, including radiologists, software engineers, ENT specialists, and 3D-printing experts. The development process spanned from June 2022 to October 2023 at the Department of Sense Organs, Sapienza University of Rome. Acquisition of human temporal bone images; temporal bone rendering; 3D-printing; post-printing phase; 3D-printed temporal bone model dissection and validation. RESULTS: The 'SAPIENS' 3D-printed temporal bone model demonstrated a high level of anatomical accuracy, resembling the human temporal bone in both middle and inner ear anatomy. The questionnaire-based assessment by five experienced ENT surgeons yielded an average total score of 49.4 ± 1.8 out of 61, indicating a model highly similar to the human TB for both anatomy and dissection. Specific areas of excellence included external contour, sigmoid sinus contour, cortical mastoidectomy simulation, and its utility as a surgical practice simulator. CONCLUSION: We have designed and developed a 3D model of the temporal bone that closely resembles the human temporal bone. This model enables the surgical dissection of the middle ear and mastoid with an excellent degree of similarity to the dissection performed on cadaveric temporal bones.

Theranostics of Thyroid Cancer.

Molecular imaging is pivotal in evaluating and managing patients with different thyroid cancer histotypes. The existing, pathology-based, risk stratification systems can be usefully refined, by incorporating tumor-specific molecular and molecular imaging biomarkers with theranostic value, allowing patient-specific treatment decisions. Molecular imaging with different radioactive iodine isotopes (ie, I131, I123, I124) is a central component of differentiated carcinoma (DTC)'s risk stratification while [18F]F-fluorodeoxyglucose ([18F]FDG) PET/CT is interrogated about disease aggressiveness and presence of distant metastases. Moreover, it is particularly useful to assess and risk-stratify patients with radioiodine-refractory DTC, poorly differentiated, and anaplastic thyroid cancers. [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT is the most specific and accurate molecular imaging procedure for patients with medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells. In addition, [18F]FDG PET/CT can be used in patients with more aggressive clinical or biochemical (ie, serum markers levels and kinetics) MTC phenotypes. In addition to conventional radioiodine therapy for DTC, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC. Moreover, peptide receptor theranostics showed promising results in patients with advanced and metastatic radioiodine-refractory DTC and MTC, respectively. The current appropriate role and future perspectives of molecular imaging and theranostics in thyroid cancer are discussed in our present review.

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

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). RESULTS: A 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). CONCLUSIONS: CCA/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.

Clinical Application of Pediatric Sleep Endoscopy: An International Survey.

OBJECTIVES: To investigate through an international survey the actual clinical application of drug-induced sleep endoscopy (DISE) in pediatric patients with obstructive sleep apnea (OSA) and to clarify the use, application, clinical indications, and protocol of pediatric DISE. METHODS: A specific survey about pediatric DISE was initially developed by five international otolaryngologists with expertise in pediatric sleep apnea and drug-induced sleep endoscopy and was later spread to experts in the field of sleep apnea, members of different OSA-related associations. RESULTS: A total of 101 participants who answered all the survey questions were considered in the study. Sixty-four sleep apnea experts, equivalent to 63.4% of interviewed experts, declared they would perform DISE in pediatric OSA patients. A total of 81.9% of responders agreed to consider the DISE as the first diagnostic step in children with persistent OSA after adenotonsillectomy surgery, whereas 55.4% disagreed with performing DISE at the same time of scheduled adenotonsillectomy surgery to identify other possible sites of collapse. In the case of young patients with residual OSA and only pharyngeal collapse during DISE, 51.8% of experts agreed with performing a velopharyngeal surgery. In this case, 27.7% disagreed and 21.4% were neutral. CONCLUSION: Pediatric DISE is internationally considered to be a safe and effective procedure for identifying sites of obstruction and collapse after adenotonsillectomy in children with residual OSA. This is also useful in cases of patients with craniofacial malformations, small tonsils, laryngomalacia or Down syndrome to identify the actual site(s) of collapse. Despite this evidence, our survey highlighted that pediatric DISE is not used in different sleep centers.

Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion.

OBJECTIVE: Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. DATA SOURCES: The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. REVIEW METHODS: Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). RESULTS: About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non-significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38-2.69), DSS (HR: 2.03; 95% CI: 0.54-7.56), and LRC (HR: 0.89; 95% CI: 0.53-1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77-0.97). CONCLUSION: The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2019-2027, 2024.

Transoral robotic surgery in oropharyngeal squamous cell carcinoma: A comparative study between da Vinci Single-Port and da Vinci Xi systems.

BACKGROUND: The recently developed da Vinci single-port (SP) system offers potential advantages in maneuverability within narrower surgical spaces. This study aims to compare intra- and post-operative outcomes, technical advantages, and limitations of transoral resections using the da Vinci SP and da Vinci Xi systems for oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A single-center retrospective cohort study included patients with OPSCC who underwent transoral robotic surgery (TORS) after neoadjuvant chemotherapy (NCT). Data on pre-operative variables, intraoperative data, postoperative complications, and functional outcomes were collected. RESULTS: A total of 209 patients (males: 175; mean age: 59.0 ± 9.3) were included (SP: n = 136; Xi: n = 73). A significantly lower docking time was measured for the SP group (5.7 ± 2.5 min vs. 10.0 ± 4.4 min; p <.001). Similarly, the console time was reduced for the SP group though not reaching statistical significance (76.3 ± 30.7 min vs. 88.1 ± 36.9 min; p =.06). A greater proportion of patients showed wide negative resection margins in the SP group (71 % vs. 56 %; p =.10), although not statistically significant. No significant differences were observed in complication rates or postoperative functional outcomes. DISCUSSION: This study demonstrates the safety and efficacy of the da Vinci SP system in oropharyngeal surgery, with potential advantages in terms of reduced docking and console times. The findings suggest that the SP system offers improved maneuverability and instrument placement compared to the da Vinci Xi system.

Development of machine learning models for the prediction of long-term feeding tube dependence after oral and oropharyngeal cancer surgery.

PURPOSE: To predict the necessity of enteral nutrition at 28 days after surgery in patients undergoing major head and neck oncologic procedures for oral and oropharyngeal cancers. MATERIAL AND METHODS: Data from 193 patients with oral cavity and oropharyngeal squamous cell carcinoma were retrospectively collected at two tertiary referral centers to train (n = 135) and validate (n = 58) six supervised machine learning (ML) models for binary prediction employing 29 clinical variables available pre-operatively. RESULTS: The accuracy of the six ML models ranged between 0.74 and 0.88, while the measured area under the curve (AUC) between 0.75 and 0.87. The ML algorithms showed high specificity (range 0.87-0.96) and moderate sensitivity (range: 0.31-0.77) in detecting patients with ≥28 days feeding tube dependence. Negative predictive value was higher (range: 0.81-0.93) compared to positive predictive value (range: 0.40-0.71). Finally, the F1 score ranged between 0.35 and 0.74. CONCLUSIONS: Classification performance of the ML algorithms showed optimistic accuracy in the prediction of enteral nutrition at 28 days after surgery. Prospective studies are mandatory to define the clinical benefit of a ML-based pre-operative prediction of a personalized nutrition protocol.

Postoperative Morbidity of Different Tonsillectomy Techniques: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To compare different tonsillectomy techniques in terms of postoperative bleeding incidence and postoperative pain. METHODS: An arm-based network analysis was conducted using a Bayesian hierarchical model. The primary and secondary outcomes were postoperative bleeding incidence and mean postoperative pain score. RESULTS: A total of 6464 patients were included for five different interventions (cold dissection tonsillectomy; extracapsular coblation tonsillectomy; intracapsular coblation tonsillectomy [ICT]; bipolar diathermy tonsillectomy [BDT]; monopolar diathermy tonsillectomy). ICT showed the lowest absolute risk (4.44%) of postoperative bleeding incidence (73.31% chance of ranking first) and the lowest mean postoperative pain score (1.74 ± 0.68) with a 94.0% chance of ranking first, whereas BDT showed both the highest absolute risk of bleeding incidence (10.75%) and the highest mean postoperative pain score (5.67 ± 1.43). CONCLUSIONS: ICT seems to offer better postoperative outcomes, in terms of reduced risk of bleeding and reduced pain. Further prospective studies are advised to confirm these findings. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1696-1704, 2024.

Predicting the need for prophylactic gastrostomy in major head and neck cancer surgery: The PEG score.

BACKGROUND: To elaborate a preoperative score to predict the necessity of enteral nutrition at 28 days postoperatively in patients undergoing head and neck surgery. METHODS: A total of 424 patients with oral cavity, oropharyngeal, laryngeal, and hypopharyngeal carcinoma were retrospectively enrolled and analyzed to identify preoperative predictors of prolonged postsurgical enteral feeding which were used to create a prediction model with an easy-to-use nomogram. RESULTS: Five preoperative variables (body mass index, previous radiotherapy, preoperative dysphagia, type of surgery, flap reconstruction) were found to be independent predictive factors and were used to create a prediction model named PEG score together with the related nomogram. Accuracy, F1, and the area under the curve (AUC) were 0.74, 0.83, and 0.74. Different decision thresholds can be used to vary the sensitivity and specificity. CONCLUSIONS: The PEG score showed high prediction performances for modeling the need for enteral nutrition at 28 days postoperatively. Prospective studies are needed to define a personalized nutrition protocol.

Near-Infrared Spectroscopy for Continuous Noninvasive Monitoring of Free Flap in Head and Neck Reconstruction: Systematic Review of the Literature and Personal Experience.

BACKGROUND: Buried free flaps represent a reconstructive challenge concerning monitoring of vitality, which is fundamental for an early detection of flap failure and prompt surgical salvage. Many flap monitoring techniques have been developed over time, and there is still no consensus concerning the best monitoring technique for buried reconstructions. METHODS: We performed a systematic review of the literature on NIRS monitoring for head and neck free flaps. Moreover, we presented a case of orbital reconstruction through a buried free myo-fascial anterolateral tight flap (ALTF) in which postoperative monitoring was performed by means of NIRS. RESULTS: Four studies were included with a total of 200 monitored head and neck free flap reconstructions. Flap survival was reported in 96.5% of studies (n = 193/200) with a 3.5% of total flap failure rate (n = 7/200). We monitored the buried myo-fascial ALTF for 7 post-operative days measuring a regional oxygen saturation (rSO2) ranging from 55% to 72% (mean = 66%). CONCLUSIONS: This device appeared to be an efficient choice for monitoring buried flaps, thanks to its ability to measure tissue perfusion deep under the skin, to the continuous availability of recorded data on the monitor, and to its low impact on the patient. Further prospective studies are advised in order to standardize this monitoring technique and define warning values.

Neo-adjuvant chemotherapy and transoral robotic surgery in locoregionally advanced oropharyngeal cancer.

PURPOSE: To analyze the oncological outcomes and patterns of recurrence of patients with locoregionally advanced oropharyngeal squamous cell carcinoma (OPSCC) who underwent neo-adjuvant chemotherapy (NCT) with subsequent transoral robotic surgery (TORS). METHODS: A single-center retrospective cohort study was performed, including 198 patients (mean age: 58.6, SD: 9.2). The primary outcome was disease-free survival (DFS). RESULTS: The median follow-up time was 26.5 months (IQR: 16.0-52.0). Estimated DFS rates (95 % CI) at 1 and 3 years were 86.6 % (81.9-91.7), and 81.4 % (75.7-87.6), respectively. Estimated DSS rates (95 % CI) at 1 and 3 years were 96.7 % (94.1-99.3), and 92.6 % (88.4-97.0), respectively. Estimated OS rates (95 % CI) at 1 and 3 years were 96.2 % (93.4-99.0), and 88.7 % (83.4-94.2), respectively. A total of 31 (15.6 %) patients showed a disease relapse after a median time of 8 months (IQR: 4.0-12.0), but only 12 (6 %) patients died of the disease during the study period. CONCLUSIONS: This study demonstrates that NCT and TORS can obtain excellent tumor control and survival in locoregionally advanced OPSCC. NCT might reduce the need for adjuvant treatments, and randomized clinical trials should be conducted to better define this aspect.

It is time to improve the diagnostic workup of oropharyngeal cancer with circulating tumor HPV DNA: Systematic review and meta-analysis.

The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16- were 269. The meta-analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82-0.94) and 0.94 (95% CI: 0.85-0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9-32.1) and 0.05 (95% CI: 0.02-0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology.

Functional outcomes of soft palate reconstruction after oncologic surgery: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to analyze functional outcomes of soft palate reconstruction after oncologic surgery. METHODS: This study was conducted in conformity with the PRISMA statement. A single arm meta-analysis was performed for feeding tube dependence (FTD) (primary outcome), velopharyngeal insufficiency (VPI) and hypernasality (HN) (secondary outcomes) incidences. RESULTS: A total of 510 patients (males: 77.75%, n = 353/454) with a median age of 58 years (n = 480/510; 95% CI 57.0-61.0) who underwent soft palate surgical resection with primary reconstruction were included. Overall, the cumulative FTD rate was 1.55% (n = 28/510; 95% CI 0.24-3.96%), the VPI rate was 22.18% (n = 119/379; 95% CI 12.99-33.02%), and the HN rate was 33.01% (n = 88/234; 95% CI 19.03-46.61%). CONCLUSIONS: Soft palate reconstruction results in a low incidence of FTD, and most patients resume a full oral diet. Both obturators, primary closure, local and free flaps seem good reconstructive options. Nevertheless, more specific postoperative functional deficiencies like VPI and HN owns higher incidences, potentially affecting the quality of the swallowing and speaking function and the patient's quality of life.

Second primary carcinoma arising on a flap: a new primary or a relapse?

BACKGROUND AND AIM: Free flaps or pedicle flaps are the mainstay of cancer surgery in the head and neck area. However, their long-term sequelae are still poorly understood. Among these, the development of a secondary primary tumor on a flap is a rare and uncertain reported event.   Methods: A computer-aided systematic literature search was performed by using the PubMed, EMBASE and Cochrane Library databases. A systematic review of the literature, following the PRISMA checklist, was carried out with the aim of analyzing all the citations reporting this second primary, with attention to risk factors, behavior, etiological causes.   Results: Overall, 27 cases of second primary squamous cell carcinoma arising on a pedicle or free flap were identified. In addition, other three cases were discussed.   Conclusions: Persistent exposure to oral stimuli such saliva, oral microbiome, smoke or a colonization by the adjacent mucosa were considered as a possible cause of second primary carcinoma. Although rare, a new neoplasm onset should know and considered as a new concept in the follow-up of patients undergoing reconstruction with free or pedicle flaps.

Current evidence on diagnosis and treatment of parotid gland lymphomas: a systematic review.

BACKGROUND AND PURPOSE: Parotid gland lymphoma (PGL) is a rare and challenging diagnosis. Different lymphomas can develop in the parotid gland, with the most common being the mucosa-associated lymphoid tissue (MALT) lymphoma, which originates directly from the glandular parenchyma. Other histologic subtypes arise from both intraglandular and extraglandular parotid lymph nodes. A consensus on diagnosis and treatment of PGL is still lacking, and published data is scarce and heterogeneous. METHODS: We performed a systematic review of the literature, including studies published after 2001, when the WHO classification of lymphoid tumours was introduced. RESULTS: Twenty retrospective studies were included in the analyses, eight of which focused exclusively on MALT lymphomas. Final analysis included 612 cases of PGL, with a 1.68:1 F/M ratio. MALT lymphoma was the most common histology, followed by follicular and diffuse large B-cell lymphoma. Most cases were low stages (IE/IIE acc. Ann Arbour, 76.5%) and only 10% of patients presented with symptoms, most commonly pain (4.8%) and B symptoms (2.2%). A high prevalence of associated autoimmune diseases was found, particularly Sjögren's syndrome, that affected up to 70% of patients with MALT lymphoma. In most cases diagnosis was achieved through parotidectomy (57.5%), or open biopsy (31.2%). Treatment strategies were either surgical, non-surgical or a combination of modalities. Surgery as a single-modality treatment was reported in about 20% of patients, supposing it might be a valuable option for selected patients. CONCLUSIONS: Our review showed that the diagnosis and treatment of PGLs is far from being standardized and needs further, more homogeneous reports to reach consensus.