A phase II open-label randomized clinical trial of preoperative durvalumab or durvalumab plus tremelimumab in resectable head and neck squamous cell carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiation based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D: 24 patients, D+T: 24 patients), 45 underwent surgical resection per protocol (D: 21 patients; D+T: 24 patients). D+/-T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast to D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D+/-T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Robot-Assisted Retroauricular Anterior Scalenectomy for Neurogenic Thoracic Outlet Syndrome.

Background: This study described the surgical technique of a robot-assisted retroauricular anterior scalenectomy and assessed clinical outcomes and complications for patients with neurogenic thoracic outlet syndrome (nTOS). Methods: Between February 2014 and August 2016, 5 patients underwent robot-assisted retroauricular anterior scalenectomy using the da Vinci Xi system for nTOS. For clinical assessment, visual analog scale (VAS) symptom score, pinch and grip strength, and disabilities of arm, shoulder and hand (DASH) score were assessed to compare preoperative and postoperative outcomes. Postoperative complications were also reviewed. Results: The VAS symptom, pinch and grip strength, and DASH scores improved 1 year after the operation. All patients were satisfied with the surgical scars. Temporary postoperative complications, which spontaneously resolved within 3 months, were noticed in 2 patients: one with vocal cord palsy and the other with upper brachial plexus palsy. Conclusions: The robot-assisted retroauricular anterior scalenectomy for patients with nTOS seems feasible and safe, providing satisfactory cosmetic results.

Surgical margin status and role of adjuvant therapy in human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: We analyzed the difference in treatment results according to safety margin range and studied the role of adjuvant therapy in patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: A total of 279 patients with HPV+ OPSCC were included in this study. RESULTS: Surgical margin and T classification were significant prognostic factors related to death. The difference in locoregional recurrence was analyzed by dividing the safety margin into groups of <1, 1-5, and >5 mm. There was no significant difference in local-regional recurrence for T1-T2 lesions between the three groups. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors. CONCLUSIONS: In T1-T2 lesions without other risk factors, even with a safety margin ≥1 mm, adjuvant therapy can potentially be omitted. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.

Robot-assisted radial forearm free flap harvesting: a propensity score-matched case-control study.

Although some surgeons prefer anterolateral thigh and latissimus dorsi flap for soft tissue reconstruction in the head and neck area because it minimizes donor site complications, the radial forearm flap remains the workhorse for soft tissue reconstruction due to its reliability. To reduce donor site morbidity, the authors developed a novel technique for radial forearm flap harvesting using a robotic device. 42 radial forearm free flap reconstruction cases were studied, consisting of 31 conventional and 11 robot-assisted cases. 1:1 propensity score matching was done according to age, sex, previous and postoperative radiation therapy history and method used for vein anastomosis. There was no significant difference in flap outcome, which was 100% vitality in the robot-assisted group and 90.9% vitality in the conventional group. The robot-assisted group showed significantly longer mean harvesting time than did the conventional group, being 107.2 min and 67.0 min, respectively. Robot-assisted radial forearm flap harvesting can reduce donor site complications by minimizing incision. When more surgical experience is gained under appropriate case selection, we expect our robot-assisted method will yield a harvesting time similar to that of the conventional method and thus become more reliable and feasible.

Investigation of somatic mutation profiles and tumor evolution of primary oropharyngeal cancer and sequential lymph node metastases using multiregional whole-exome sequencing.

Lymph node (LN) metastasis is an important factor in determining the treatment and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Here, we compared the somatic mutational profiles and clonal evolution of primary and metastatic LNs using multiregion sequencing of human papilloma virus (HPV)-positive OPSCC and HPV-negative OPSCC. We performed high-depth whole-exome sequencing (200×) of 76 samples from 18 patients with OPSCC (10 HPV-positive and 8 HPV-negative), including 18 primary tumor samples, 40 metastatic LN samples, and 18 normal tissue samples. Among 40 metastatic LNs, 22 showed extranodal extension (ENE). Mutation profiles of HPV-positive OPSCC and HPV-negative OPSCC were similar to those reported previously. Somatic mutations in CDKN2A and TP53 were frequently detected in HPV-negative OPSCC. Somatic mutations in HPV-positive OPSCC samples showed APOBEC-related signatures. Somatic mutations from metastatic LNs showed a different pattern than the primary tumor. Somatic mutations acquired in the WNT pathway during metastasis showed a significant relationship with ENE. Clonal evolution analysis of primary and metastatic LNs showed that, in some cases, each metastatic LN originated from a different primary tumor sub-clone.

Comparing Free-Flap Reconstruction After Robot-Assisted Neck Dissection via a Retroauricular Approach and a Traditional Transcervical Approach: Single-Surgeon Experiences of 90 Consecutive Cases.

BACKGROUND: Predominant traditional approaches for most patients who have advanced-stage oral cancer with transcervical incision lines left irreversible scars. To address this, surgeons have continuously refined minimally invasive surgery (MIS) techniques, including robot-assisted neck surgeries. This article introduces and discusses the feasibility, versatility, and availability of free-flap reconstruction via the retroauricular approach (RA), considered difficult to date. METHODS: This study retrospectively analyzed 90 consecutive patients who had free-flap reconstruction performed by a single surgeon (D.K.) in the Department of Oral and Maxillofacial Surgery, Yonsei University, from March 2021 to April 2022. The type of defects and flaps, hospitalization days, total operation time, and type of vessels and anastomoses were compared statistically. RESULTS: The type of vessels used did not differ between the RA and the transcervical approach (TA) groups, nor in duration of hospital stays. Likewise, the total reconstruction time did not differ significantly between the TA group (240 min) and the RA group (245 min) (p = 0.756). However, the total operation time was about 1 h less in the TA group, a statistically significant difference (TA group [593 ± 152 min] vs. RA group [655 ± 117 min]; p = 0.044). All flaps were successful in the RA group, whereas one flap in the TA group led to a total loss (TA group [98.3%] vs. RA group [100.0%]; p = 1.000). CONCLUSIONS: Even for patients with advanced oral cancer who require massive tumor ablation, it is feasible to obtain an aesthetic and functional surgical outcome by performing free-flap reconstruction via the retroauricular approach.

Treatment outcomes and radiotherapy deintensification strategies in human papillomavirus-associated tonsil cancer.

BACKGROUND: Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies. METHODS: A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson's chi-square or Fisher's exact test was used to compare categorical variables, and Student's t-test was used to compare continuous variables. The Kaplan-Meier method and log-rank test were used to assess overall survival, progression-free survival, and locoregional failure (LRF). RESULTS: No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who underwent primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF. CONCLUSIONS: Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered.

Characterizing intrinsic molecular features of the immune subtypes of salivary mucoepidermoid carcinoma.

INTRODUCTION: Characterizing the tumor microenvironment (TME) and immune landscape of cancer has been a promising step towards discovering new therapeutic biomarkers and guiding precision medicine; however, its application in mucoepidermoid carcinoma (MEC) has been sparse. Here, we conducted a comprehensive study to understand the properties of the TME and immune profiles of MEC. METHOD: 20 patients with MEC were collected from Yonsei Head and Neck Cancer Centre, Yonsei University, South Korea. Total RNA sequencing was conducted to determine gene expression profiles. Bioinformatic and immunoinformatic analyses were applied to characterize the TME and identify immunophenotypic subgroups, and to investigate the molecular features that explain the distinct phenotypes. RESULTS: The MEC samples were subdivided into two groups, immune hot and immune cold, based on the heterogenous immune cell-infiltration and activation level. The immune-hot subgroup exhibited a higher level of immune activity, including T cell infiltration, cytolytic score, IFN-γ, antigen-presenting machinery, and immune modulator genes. Further characterizing molecular features of two subgroups, downregulation of lipid metabolic regulators, including MLXIPL and FASN, and the migration of chemokines and leukocytes were observed, respectively. And, Group-specific expression of immune checkpoint molecules, such as TIGIT, PD-L2, and CTLA-4, was observed in the immune-hot group, which can be exploited as a potential immunotherapeutic biomarker. CONCLUSIONS: Immunophenotypically heterogeneous MEC subgroups analysis has shown distinctive molecular characteristics and provided potential treatment options. These findings yield new insights into TME of MEC and may help next step to study this uncharted cancer.

Methodology in Conventional Head and Neck Reconstruction Following Robotic Cancer Surgery: A Bridgehead Robotic Head and Neck Reconstruction.

PURPOSE: Robotic head and neck surgery is widespread nowadays. However, in the reconstruction field, the use of robotic operations is not. This article aimed to examine methodologies for conventional head and neck reconstruction after robotic tumor surgery in an effort to obtain further options for future reconstruction manipulations. MATERIALS AND METHODS: A retrospective review of all patients who received head and neck robot surgery and conventional reconstructive surgery between October 2016 and September 2021. RESULTS: In total, 53 cases were performed. 67.9% of the tumors were greater than 4 cm. Regarding defect size, 47.2% of the lesions were greater than 8 cm. In terms of TNM stage, stage 3 disease was recorded in 26.4% and stage 4 in 52.8%. To make a deep and narrow field wider, we changed the patient's posture in pre-op field, additional dissection was done. We used radial forearm flap mostly (62.2%). CONCLUSION: Conventional head and neck reconstruction after robotic ENT cancer surgery is possible. One key step is to secure additional space in the deep and narrow space left after robotic surgery. For this, we opted for a radial forearm flap mostly. This can be performed as a bridgehead to perform robotic head and neck reconstruction.

Robot-Assisted Total Thyroidectomy with or without Robot-Assisted Neck Dissection in Pediatric Patients with Differentiated Thyroid Cancer.

Pediatric thyroid cancer more frequently develops cervical node metastasis than adult thyroid cancer, even in differentiated thyroid carcinoma (DTC). Thus, cervical neck dissection often needs to be performed simultaneously with thyroidectomy in pediatric patients. Herein, we describe our experience with robot-assisted total thyroidectomy with/without robot-assisted neck dissection in pediatric patients compared with the conventional operated group. A total of 30 pediatric patients who underwent thyroidectomy for DTC between July 2011 and December 2019 were retrospectively reviewed. Among them, 22 underwent robot-assisted operation, whereas 8 underwent conventional operation. There was no statistical difference in the mean operation times, blood loss, drainage amounts, and hospital stay length between the robot-assisted and conventional operation groups; however, the operation time was less in the retroauricular approach subgroup (robot-assisted operation group) with better satisfaction on cosmesis. No postoperative complications, such as seromas, hemorrhages, or hematomas were observed. Our experience suggested that robot-assisted thyroidectomy with or without neck dissection through the retroauricular approach is a feasible and safe alternative treatment, producing outstanding esthetic results compared to the conventional approach, especially in pediatric patients with DTC.

Phase II Clinical Trial of Eribulin-Gemcitabine Combination Therapy in Previously Treated Patients With Advanced Liposarcoma or Leiomyosarcoma.

PURPOSE: Monotherapy with eribulin or gemcitabine has been found to be moderately effective in treating soft-tissue sarcomas (STS). In this study, we evaluated the efficacy and safety of eribulin-gemcitabine combination therapy for the two most common histologic types of STS, liposarcoma and leiomyosarcoma. PATIENTS AND METHODS: In this nonrandomized, multicenter, phase II study, we included patients with progressive disease who had received one or two courses of chemotherapy that included doxorubicin. Patients were administered 1.4 mg/m2 eribulin and 1,000 mg/m2 gemcitabine on days 1 and 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks), with null and alternative hypotheses of PFSR12wks ≤20.0% and ≥40.0%, respectively. Exploratory biomarker analyses with next-generation sequencing (NGS) were performed on pretreatment tumor samples. RESULTS: Among the 37 patients included, the overall PFSR12wks was 73.0%, achieving the primary endpoint. The objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 5.6 months, and 31.9 months, respectively, without differences according to histologic type. New safety signals and treatment-related deaths were not documented. NGS-based transcriptome analysis revealed that functional enrichment in the TGFß pathway was mostly associated with a poor outcome, whereas single genetic alterations largely failed to predict treatment outcome. CONCLUSIONS: Eribulin-gemcitabine combination therapy showed promising activity and an acceptable safety profile in patients with liposarcoma or leiomyosarcoma. Gene expression profiling with pathway enrichment analysis would have possibilities to have predictive value for survival outcome, necessitating further investigation to confirm.

Deep learning model for tongue cancer diagnosis using endoscopic images.

In this study, we developed a deep learning model to identify patients with tongue cancer based on a validated dataset comprising oral endoscopic images. We retrospectively constructed a dataset of 12,400 verified endoscopic images from five university hospitals in South Korea, collected between 2010 and 2020 with the participation of otolaryngologists. To calculate the probability of malignancy using various convolutional neural network (CNN) architectures, several deep learning models were developed. Of the 12,400 total images, 5576 images related to the tongue were extracted. The CNN models showed a mean area under the receiver operating characteristic curve (AUROC) of 0.845 and a mean area under the precision-recall curve (AUPRC) of 0.892. The results indicate that the best model was DenseNet169 (AUROC 0.895 and AUPRC 0.918). The deep learning model, general physicians, and oncology specialists had sensitivities of 81.1%, 77.3%, and 91.7%; specificities of 86.8%, 75.0%, and 90.9%; and accuracies of 84.7%, 75.9%, and 91.2%, respectively. Meanwhile, fair agreement between the oncologist and the developed model was shown for cancer diagnosis (kappa value = 0.685). The deep learning model developed based on the verified endoscopic image dataset showed acceptable performance in tongue cancer diagnosis.

Current Issues in Treatment of Parotid Gland Cancer and Advanced Surgical Technique of Robotic Parotidectomy.

PURPOSE OF REVIEW: This paper analyzed previous research data to identify the most important issues to be considered during treatment of parotid gland cancer (PGC) and reviewed recent advancements in techniques in parotid surgery. RECENT FINDINGS: For successful treatment of PGC, a preoperative surgical plan should be designed with consideration of the histologic characteristics and anatomical complexity of the tumor, and the functional and anatomical integrity of the facial nerve should be carefully inspected during surgery and damage to the nerve minimized. The need for adjuvant radiotherapy should be determined based on intraoperative findings and pathologic findings of the specimen after surgery. Surgery and radiotherapy are the main treatment options for PGC. To optimize treatment outcomes for PGC, the extent of surgery should be decided according to histologic characteristics and extent of tumor resection, and use of adjuvant radiotherapy should be considered based on risk stratification.

Machine learning and magnetic resonance imaging radiomics for predicting human papilloma virus status and prognostic factors in oropharyngeal squamous cell carcinoma.

BACKGROUND: We attempted to predict pathological factors and treatment outcomes using machine learning and radiomic features extracted from preoperative magnetic resonance imaging (MRI) of oropharyngeal squamous cell carcinoma (OPSCC) patients. METHODS: The medical records and imaging data of 155 patients who were diagnosed with OPSCC were analyzed retrospectively. RESULTS: The logistic regression model showed that the area under the receiver operating characteristic curve (AUC) of the model was 0.792 in predicting human papilloma virus (HPV) status. The LightGBM model showed an AUC of 0.8333 in predicting HPV status. The performance of the logistic model in predicting lymphovascular invasion, extracapsular nodal spread, and metastatic lymph nodes showed AUC values of 0.7871, 0.6713, and 0.6638, respectively. In predicting disease recurrence, the LightGBM model showed an AUC of 0.8571. In predicting patient death, the logistic model showed an AUC of 0.8175. CONCLUSIONS: A machine learning model using MRI radiomics showed satisfactory performance in predicting pathologic factors and treatment outcomes of OPSCC patients.

Recent progress of robotic head and neck surgery using a flexible single port robotic system.

We performed robotic neck surgery through a transoral or retroauricular approach (RA) using the DaVinci SP and analyzed our experiences to evaluate the feasibility and safety of this system for performing RA neck surgeries. A total of 63 patients were enrolled in this study, consisting of 37 males and 26 females. All operations were successfully completed without significant complication in 63 patients with head and neck tumor. Using DaVinci SP, it is easy to insert three robotic arms into a long and narrow working space because all robotic arms and an endoscope are inserted through a single arm. Using the navigation function of the DaVinci SP, the endoscopic arm could be made into the shape of a "cobra" to secure proper visualization of the surgical site, which helps surgeons identify specific anatomic structures such as cranial nerve or vessels. We did not have any cases where robotic surgery was converted to open surgery due to severe bleeding or technical issues during surgery. The mean operative time was 207 min and the average hospital stay was 6.9 days. The time required for docking the surgical robot was within 10 min on average for DaVinci SP, which was much simpler and faster than that of the previous Si/Xi system. Based on our early experiences performing robotic head and neck surgery using the DaVinci SP, we confirmed that the system provided advanced technical advantages over the previous Si/Xi system in performing robotic surgery.

Treatment outcomes of neoadjuvant chemotherapy and transoral robotic surgery in locoregionally advanced laryngopharyngeal carcinoma.

BACKGROUND: We aimed to identify the optimal indications of neoadjuvant chemotherapy (NACT) and transoral robotic surgery (TORS) in patients with locoregionally advanced (T3-4 or N2-3) head and neck cancer (HNC). METHODS: A total of 50 patients were included in the study. RESULTS: T1 was identified in seven cases, T2 in 19, T3 in 22, and T4 in 2. N0 was identified in nine cases, N1 in 18, N2 in 22, and N3 in 1. There were 25 patients (50%) with complete remission of the primary lesion and 25 patients (50%) with partial remission. On pathologic examination of surgical specimens after neoadjuvant chemotherapy and TORS, 2 patients (4%) had a positive surgical margin, and 48 patients (96%) had a negative margin. Pathologic metastatic lymph nodes (LNs) were not observed in 39 cases (78%), and one metastatic LN was observed in 11 cases (22%). The 3-year recurrence-free survival (RFS) of all patients was 85.4%. On multivariate analysis, lymphovascular invasion showed a significant correlation with RFS. CONCLUSIONS: In patients with locoregionally advanced HNC, NACT and TORS achieved favorable oncologic and functional outcomes.