Oropharyngeal Tumors Research Articles

Abstract B013: Development of oropharyngeal tumor organoids for disease modeling and high throughput drug screening

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with approximately 550,000 new cases diagnosed each year. The oropharynx is one of the most common sites of occurrence, and disease in this region most often presents in the palatine tonsil, followed by the base of tongue and soft palate. Human papilloma virus (HPV) is a common cause of HNSCC, giving rise to a distinct subset of tumors with a different clinical presentation, disease course, and response to treatment. In order to further characterize HPV+ HNSCC tumors and their therapy response, we have leveraged our high throughput 3D tumor organoid screening platform. Our approach entails seeding tumor cells in extracellular matrix gels deposited around the perimeter of tissue culture wells in ring-like structures, with screening results available within a week from surgery (Phan et al, 2019; Al Shihabi et al, 2022; Nguyen et al, 2022; Al Shihabi et al 2023). We particularly focused on tonsil tumors, and develop organoids from both HNSCC and contralateral normal tonsil tissue. Thus far, we have procured tonsil samples from 31 patients to develop organoids, perform high throughput drug screening, and immunohistochemical characterization including H&E staining, Ki67, p16 and p53 immunohistochemical staining. We have leveraged dynamic optical contrast imaging (DOCI), a label-free tissue autofluorescence imaging method that is being investigated clinically (Kim et al, 2017), to assist in distinguishing tumor organoids from normal tissue organoids. Lastly, given the importance of radiation as a treatment modality for HPV+ HNSCC, we have also optimized a chemoradiation pipeline to test possible combinatorial effects. Taken together, our results demonstrate that 3D organoids of HNSCC generated from patient samples can successfully preserve native tissue characteristics and can be used for high throughput drug screening and radiation de-escalation testing, affording critical insight into the management of HNSCC in patients. Citation Format: Krishna K. Bommakanti, Luda Lin, Yazeed Alhiyari, Andreanne Sannajust, Brandon Mo, Lauran Evans, Peyton Tebon, Maie St. John, Alice Soragni. Development of oropharyngeal tumor organoids for disease modeling and high throughput drug screening [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B013.

Impact of pretreatment body mass index on the survival of head and neck cancer patients.

Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite. Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival. BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors. This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted.

The Value of the Endoscope-Holding Arm in Transoral Pharyngeal Surgery.

Transoral pharyngeal surgery is mainly feasible with the use of a microscope or robotic systems. Data about alternative methods, with lower costs and easier availability, are sparse. We intended to examine to what extent the endoscope-holding arm is a suitable alternative to the microscope or robotic systems. We retrospectively reviewed subjects who underwent pharyngeal tumor resection with the endoscope-holding arm in our university department. We identified 13 subjects who underwent transoral pharyngeal surgery between November 2020 and November 2023. Most subjects presented with an oropharyngeal tumor (6/11 in the lateral wall or tonsil; 4/11 in the tongue base). The oropharyngeal lateral wall or tonsillar tumors were exposed with a standard mouth gag. The tongue-base tumors or hypopharyngeal tumors were exposed with an operating laryngoscope. Advantages over the microscope included an angled view. Advantages over robotic systems included haptic feedback and a faster setup. Advantages over both the microscope and robotic systems included lower costs and easier availability. Visualization with the endoscope was sufficient and similar to that of the microscope. Bimanual action was possible with surgical forceps and a monopolar electrode. Transoral pharyngeal surgery was feasible with the endoscope-holding arm. The endoscope-holding arm could be a cost-efficient alternative to the microscope or robotic systems.

Identification and Quantification of Radiotherapy-related Protein Expression in Cancer Tissues Using the Qupath Software and Prediction of Treatment Response.

Automated measurement of immunostained samples can enable more convenient and objective prediction of treatment outcome from radiotherapy. We aimed to validate the performance of the QuPath image analysis software in immune cell markers detection by comparing QuPath cell counting results with those of physician manual cell counting. CD8- and FoxP3-stained cervical, CD8-stained oropharyngeal, and Ku70-stained prostate cancer tumor sections were analyzed in 104 cervical, 92 oropharyngeal, and 58 prostate cancer patients undergoing radiotherapy at our Institution. QuPath and manual counts were highly correlated. When divided into two groups using ROC curves, the agreement between QuPath and manual counts was 89.4% for CD8 and 88.5% for FoxP3 in cervical cancer, 87.0% for CD8 in oropharyngeal cancer and 80.7% for Ku70 in prostate cancer. In cervical cancer, the high CD8 group based on QuPath counts had a better prognosis and the low CD8 group had a significantly worse prognosis [p=0.0003; 5-year overall survival (OS), 65.9% vs. 34.7%]. QuPath counts were more predictive than manual counts. Similar results were observed for FoxP3 in cervical cancer (p=0.002; 5-year OS, 62.1% vs. 33.6%) and CD8 in oropharyngeal cancer (p=0.013; 5-year OS, 80.2% vs. 47.2%). In prostate cancer, high Ku70 group had worse and low group significantly better outcome [p=0.007; 10-year progression-free survival (PFS), 56.0% vs. 93.8%]. QuPath showed a strong correlation with manual counting, confirming its utility and accuracy and potential applicability in clinical practice.

Non-invasive diagnosis of upper airway malignancies based on the analysis of markers in exhaled air

The purpose of the study was to evaluate diagnostic capabilities of the gas analysis sensor device used for the study of exhaled gas samples obtained from patients with oropharyngeal and laryngeal cancers.Material and Methods. Exhaled gas samples from 31 oropharyngeal and laryngeal cancer patients and 31 healthy volunteers were studied using a diagnostic device based on the detection of volatile compounds in inhaled air using semiconductor gas sensors with subsequent neural network analysis.Results. Based on the signals from gas sensors, the neural network classified and identified patients with malignant neoplasms. The sensitivity and specificity of the method were 67.74% and 87.1%, respectively.Conclusion. The gas analysis sensor device and the method for detecting oropharyngeal and laryngeal tumors using the exhaled gas analysis are an accessible and cheap diagnostic tools, and are promising for screening the population in order to select individuals for a comprehensive examination (endoscopic, radiological and morphological) in identifying suspicion of cancer.

41. Oral and Maxillofacial Surgery experience in Transoral Robotic Surgery for oropharyngeal tumour

41. Oral and Maxillofacial Surgery experience in Transoral Robotic Surgery for oropharyngeal tumour

Comorbidities and Laryngeal Cancer in Patients with Obstructive Sleep Apnea: A Review.

Introductions: The global prevalence of obstructive sleep apnea shows that this disease appears in 1 billion people, with the prevalence exceeding 50% in some countries. Treatment is necessary to minimize negative health impacts. Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that reduced activity in the upper airway muscles plays a significant role in its onset. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, and cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. This is a review of the subject of OSA that considers several aspects: an analysis of the comorbidities associated with OSA, the involvement of tumor pathology in the onset of OSA, and the association of OSA with various types of laryngeal cancers. Additionally, it includes an evaluation of postoperative and medical outcomes for patients with OSA and laryngeal tumors treated surgically and medically, including chemotherapy. Relevant Sections: By taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing the PubMed, Medline, and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, and chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Discussions: The review evaluates the involvement of OSA in the presence of comorbidities, as well as the increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions: The studies regarding the correlations between OSA, comorbidities, and head and neck tumors indicate a significantly increased risk of OSA in association with conditions such as diabetes, metabolic syndrome, cardiovascular diseases, and head and neck tumors, particularly laryngeal tumors. This association has a physio-pathological basis. The various surgical methods followed by radiation and chemotherapy for tumor treatment do not exclude an increased risk of developing OSA after treatment. This significantly influences the quality of life of patients who survive these types of tumors. Future directions: Due to the multiple comorbidities associated with OSA, the extension of polysomnography associated with investigations during sleep, such as drug-induced sleep endoscopy, represents a tendency for the early diagnosis of this pathology, which affects the quality of life of these patients. Patients with head and neck cancer are at high risk of developing obstructive sleep apnea; this is why it is necessary to expand the polysomnographic investigation of these patients after surgical procedures or after radiotherapy and chemotherapy.

Management of Synchronous Locally Advanced Carcinoma Oropharynx and Early Stage Carcinoma Esophagus in a Tertiary Cancer Center: A Case Report

Risk factors for squamous cell carcinomas (SCCs) of the head and neck (HN) and oesophagus are similar. As such, synchronous primary tumors in these areas are not entirely uncommon. Definitive chemoradiation (CRT) is standard care for locally advanced HNSCC and is a preferred option for inoperable oesophageal SCC. Simultaneous treatment of both primaries with CRT can present technical challenges. We report a case of synchronous oropharyngeal and oesophageal SCC primary tumors treated simultaneously with definitive chemoradiotherapy.&#x0D;

Long-read sequencing of oropharyngeal squamous cell carcinoma tumors reveal diverse patterns of high-risk Human Papillomavirus integration.

In North America and in most European countries, Human Papillomavirus (HPV) is responsible for over 70% of oropharyngeal squamous cell carcinomas. The burden of OPSCC, in high-income countries, has been steadily increasing over the past 20 years. As a result, in the USA and in the UK, the burden of HPV-related oropharyngeal squamous cell carcinoma in men has now surpassed that of cervical cancer in women. However, the oncogenic impact of high-risk HPV integration in oropharyngeal squamous cell carcinomas hasn't been extensively studied. The present study aimed to explore the patterns of HPV integration in oropharyngeal squamous cell carcinomas and to assess the feasibility and reliability of long-read sequencing technology in detecting viral integration events in oropharyngeal head and neck cancers. A cohort of eight HPV-positive OPSCC pre-treatment patient tumors (four males and four females), were selected. All patients received a p16INK4A positive OPSCC diagnosis and were treated at the McGill University Health Centre, a quaternary center in Montreal. A minimum of 20mg of tumor tissue was used for DNA extraction. Extracted DNA was subjected to Nanopore long-read sequencing to detect and analyze for the presence of high-risk HPV sequences. PCR and Sanger sequencing experiments were performed to confirm Nanopore long-read sequencing readings. Nanopore long-read sequencing showed that seven out of eight patient samples displayed either integrated or episomal high-risk HPV sequences. Out of these seven samples, four displayed verifiable integration events upon bioinformatic analysis. Integration confirmation experiments were designed for all four samples using PCR-based methods. Sanger sequencing was also performed. Four distinct HPV integration patterns were identified: concatemer chromosomal integration in a single chromosome, bi-chromosomal concatemer integration, single chromosome complete integration and bi-chromosomal complete integration. HPV concatemer integration also proved more common than full HPV integration events. Long-read sequencing technologies can be effectively used to assess HPV integration patterns in OPSCC tumors. Clinically, more research should be conducted on the prognostication value of high-risk HPV integration in OPSCC tumors using long-read sequencing technology.

Fetal Oropharyngeal Teratoma: A Rare Tumour: A Case Report

Teratomas generally constitute 25-30% of congenital tumours with oropharyngeal tumours being very rare. The tumor typically arises from the palato-pharyngeal region around the basishenoid. Incidence is in 1 in 35,000-200,000 of live births. Most head and neck teratomas are incidental findings on routine second-trimester ultrasonography and are usually associated with polyhydramnios in 40% of cases. This case was also diagnosed with fetal oropharyngeal tumour at 20 weeks USG and was associated with polyhydramnios. After counselling, couple opted for termination of pregnancy in view of poor prognosis. After expulsion, products of conception were sent for histopathology and karyotyping.

Importance of tumor volume, overall treatment time and fractionation sensitivity for p16-positive and p16-negative oropharyngeal tumors

Background Analyses of clinical outcomes following radiotherapy (RT) have advanced our understanding of fundamental radiobiological characteristics in head and neck squamous cell carcinoma (HNSCC). Low fractionation sensitivity appears to be a common feature, as well as susceptibility to changes in overall treatment time (OTT). Large tumors should be harder to cure if a successful RT requires the sterilization of all clonogenic cells. Congruently, primary tumor volume has proven to be an important parameter. However, most findings come from an era when p16-negative HNSCC was the dominant tumor type. HPV-associated, p16-positive, oropharyngeal tumors (OPSCC) are more radiosensitive and have better outcome. The current study aims to investigate the role of primary tumor volume, OTT and estimate α-ratio for p16-positive OPSCC, and to quantify the differences in radiosensitivity depending on p16-status. Methods A cohort of 523 patients treated with RT was studied using a tumor control probability (TCP)-model that incorporates primary tumor volume (V) raised to an exponent c, OTT and α-estimation. The significance of V was also investigated in Cox-regression models. Results In the p16-positive cohort (n = 433), the volume exponent was 1.44 (95%CI 1.06–1.91), compared to 0.90 (0.54–1.32) for p16-negative tumors (n = 90). Hazard ratios per tumor volume doubling were 2.37 (1.72–3.28) and 1.83 (1.28–2.62) for p16-positive and p16-negative, respectively. The estimated α-ratio was 9.7 Gy (−2.3–21.6), and a non-significant daily loss of 0.30 Gy (−0.17–0.92) was found. An additional dose of 6.8 Gy (interquartile range 4.8-9.1) may theoretically counteract the more radioresistant behavior of p16-negative tumors. Conclusion Primary tumor volume plays a crucial role in predicting local tumor response, particularly in p16-positive OPSCC. The estimated α/β-ratio for p16-positive oropharyngeal tumors aligns with previous HNSCC studies, whereas the impact of prolonged OTT was slightly less than previously reported. The differences in radiosensitivity depending on p16-status were quantified. The findings should be validated in independent cohorts.

An Intensive 18F-Fludeoxyglucose–Positron Emission Tomography With Computed Tomography–Based Strategy of Follow-Up in Patients Treated for Head and Neck Squamous Cell Carcinoma Who Are Clinically Asymptomatic

Patients with head and neck squamous cell carcinoma (HNSCC) have a significant risk of locoregional recurrence within the first 2 years, with approximately two-thirds of patients experiencing such recurrence. While early recurrence detection may be associated with improved patient outcomes, the association of such detection with survival remains uncertain. To investigate the association of an intensive posttreatment follow-up strategy using 18F-fludeoxyglucose-positron emission tomography with computed tomography (18FDG-PET/CT) with survival among patients with HNSCC. This case-control study was conducted among patients treated at 1 of 3 locations in Brest, France (University Hospital, Military Hospital, or Pasteur Clinic). The statistical analysis was conducted from January to June 2023. All adults with histologically proven HNSCC who were treated with curative intent between January 1, 2006, and December 31, 2019, and achieved a complete response on imaging at 3 to 6 months were included. They had a minimum of 3 years of follow-up. Patients undergoing an intensive posttreatment follow-up strategy had 18FDG-PET/CT (PET/CT group) at months 12, 24, and 36, chosen at the discretion of ear, nose, and throat surgeons. Overall survival (OS) at 3 years. Among 782 patients with HNSCC (642 males [82.1%]; median [IQR] age, 61 [56-68] years), 497 patients had 18FDG-PET/CT during follow-up and 285 patients had conventional follow-up (CFU group). Cox regression analysis showed an association between undergoing 18FDG-PET/CT and lower risk of death (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002) after adjustment for covariates (age, sex, comorbidities, primary location, stage, surgeon, year of treatment, and treatment). The mean (SD) 3-year OS was significantly better in the PET/CT vs CFU group (72.5% [2.0%] vs 64.3% [2.9%]; P = .002). Analysis based on American Joint Committee on Cancer stage showed significantly better mean (SD) 3-year OS for advanced stages III and IV in the PET/CT group (373 patients) vs CFU group (180 patients; 68.5% [2.4%] vs 55.4% [3.8%]; P < .001), while no significant difference was observed between patients with stage I or II HNSCC. Analysis based on primary tumor site revealed significantly longer mean (SD) 3-year OS for oropharyngeal tumor in the PET/CT group (176 patients) than the CFU group (100 patients; 69.9% [3.5%] vs 60.5% [5.0%]; P = .04). This case-control study found that use of 18FDG-PET/CT in the standard annual CFU of HNSCC was associated with a 3-year survival benefit, with a larger benefit for patients with advanced initial tumor stage (III-IV) and oropharyngeal disease.

Pretreatment pain predicts perineural invasion in patients with head and neck squamous cell carcinoma.

Perineural invasion (PNI) in head and neck cancer (HNC) is a distinct pathological feature used to indicate aggressive tumor behavior and drive treatment strategies. Our study examined the prevalence and predictors of PNI in HNC patients stratified by tumor site. A retrospective analysis of head and neck squamous cell carcinoma (HNSCC) patients who underwent surgical resection at the University of Pittsburgh Medical Center between 2015 and 2018 was performed. Pretreatment pain was assessed at least 1 week before surgery using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). Demographics, clinical characteristics, and concomitant medications were obtained from medical records. Patients with cancers at the oropharynx and non-oropharynx (i.e., cancer at oral cavity, mandible, larynx) sites were separately analyzed. Tumor blocks were obtained from 10 patients for histological evaluation of intertumoral nerve presence. A total of 292 patients (202 males, median age = 60.94 ± 11.06) were assessed. Pain and PNI were significantly associated with higher T stage (p < 0.001) and tumor site (p < 0.001); patients with non-oropharynx tumors reported more pain and had a higher incidence of PNI compared to oropharynx tumors. However, multivariable analysis identified pain as a significant variable uniquely associated with PNI for both tumor sites. Evaluation of nerve presence in tumor tissue showed 5-fold higher nerve density in T2 oral cavity tumors compared to oropharyngeal tumors. Our study finds that PNI is associated with pretreatment pain and tumor stage. These data support the need for additional research into the impact of tumor location when investigating targeted therapies of tumor regression.

Phase 2 trial of retifanlimab (anti–PD-1) in combination with INCAGN02385 (anti–LAG-3) and INCAGN02390 (anti–TIM-3) as first-line treatment in patients with PD-L1–positive recurrent/metastatic squamous cell carcinoma of the head and neck.

TPS6104 Background: Anti–PD-(L)1 therapies have improved clinical outcomes in PD-L1+ squamous cell carcinoma of the head and neck (SCCHN). However, many patients either do not respond or develop resistance, partly due to additional immune checkpoint receptors including LAG-3 and TIM-3, which are frequently coexpressed with PD-1 on tumor-infiltrating lymphocytes. In preclinical studies, LAG-3 and TIM-3 blockade showed synergistic activity with PD-1 inhibition, and triple blockade improves T-cell reinvigoration and antitumor efficacy over single/double combinations. Emerging clinical evidence also supports blockade of PD-1, LAG-3, and TIM-3 as a promising combination approach in checkpoint inhibitor–naive patients. This study aims to assess the efficacy and safety of the anti–PD-1 antibody, retifanlimab, in combination with INCAGN02385 (anti–LAG-3) and INCAGN02390 (anti–TIM-3) antibodies as first-line treatment in PD-L1+ recurrent or metastatic SCCHN. Methods: This randomized, double-blind, multicenter, phase 2 study (NCT05287113) includes patients with previously untreated, recurrent or metastatic, PD-L1+ (combined positive score [CPS] ≥1%) SCCHN and ECOG status of 0 or 1. Approximately 162 patients will be randomized 1:1:1 to receive (1) intravenous (IV) retifanlimab 500 mg every 4 weeks (Q4W) plus placebo controls, (2) retifanlimab plus IV INCAGN02385 350 mg Q2W plus placebo, or (3) retifanlimab plus INCAGN02385 plus IV INCAGN02390 400 mg Q2W. Patients will be stratified at randomization by LAG-3 expression (tumor proportion score ≥5% vs &lt; 5%), PD-L1 CPS (1%-19% vs ≥20%), and human papillomavirus p16 status (positive vs negative; oropharyngeal tumors only). Treatment will be administered in 4-week cycles for up to 2 years. The primary endpoint is progression-free survival (PFS; defined per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1). Secondary endpoints are objective response rate per RECIST v1.1, duration of response, disease control, overall survival, and safety. Sample size calculation is based on a median PFS of 3 months, based on historical data for anti–PD-1 monotherapy in the first-line treatment setting for PD-(L)1+ advanced/metastatic SCCHN. PFS, overall survival, and duration of response data will be analyzed by the Kaplan-Meier method. Patient enrollment is ongoing. Clinical trial information: NCT05287113 .

Robotic surgery in pharyngolaryngeal cancer and sleep apnea syndrome: Our experience

Head and neck cancer is a complex pathology whose incidence has increased in recent years. The primary treatment is surgery, which involves extensive and mutilating interventions through the cervical region, leaving significant anatomofunctional sequelae. Since 2009, the use of robotic surgery using the Da Vinci® system has been consensus for resecting oropharyngeal and supraglottic tumors through transoral surgery. Subsequently, its utility has also been observed in the surgery of patients with Sleep Apnea Syndrome (SAS). The advantages of this technique are based on the improved and early recovery of the patients. This article presents our experience in the management and postoperative care of this surgical technique for both oncological pathology and sleep apnea pathology.

Taste changes during radiotherapy for head and neck cancer

IntroductionTaste changes (dysgeusia) during radiotherapy for head and neck cancer are associated with malnutrition, tube feeding and reduced toleration of treatment. MethodThe MD Anderson symptom inventory – head and neck (MDASI-HN) questionnaire was completed by patients in a single department receiving radical radiotherapy or chemo-radiotherapy for head and neck cancer during weeks 1 and 4 of radiotherapy. Participants who developed dysgeusia in week 4 completed supplementary questions exploring what foods they could taste and how they managed taste changes. ResultsAt week 4, 97% of 61 participants reported taste changes, 77% reporting moderate or severe changes. 30% of participants reported taste changes during week 1. Patients with oropharyngeal, oral cavity and parotid gland tumours were most likely to develop dysgeusia. Females were more likely than males to report taste changes. A soft, semi-liquid diet was reportedly easier to tolerate as the more food was chewed the worse the taste became. ConclusionsPatients having radiotherapy for all head and neck cancers should be warned of the very high risk of developing taste changes and the time scale for this. Patients with taste changes should be advised a softer diet requiring less chewing will be better tolerated. The finding that females are more at risk than males of dysgeusia needs further investigation. Implications for practicePatients with head and neck cancer should expect taste changes from the start of radiotherapy. Patients with dysgeusia should be advised that soft, semi-liquid foods that require less chewing before swallowing are easier to tolerate and that taste changes day-to-day.

Radiotherapy-Dose Escalated for Large Volume Primary Tumors-And Cetuximab with or without Induction Chemotherapy for HPV Associated Squamous Cell Carcinoma of the Head and Neck-A Randomized Phase II Trial.

Eligible patients in this multicenter, randomized, controlled, phase 2 trial had p16-positive locoregionally advanced SCCHN. Patients were randomized in a 1:1 ratio to either RT with cetuximab (arm B) versus the same regimen preceded by two cycles of taxotere/cisplatin/5-FU (arm A). The RT dose was escalated to 74.8 Gy for large volume primary tumors. Eligibility criteria included patients of 18-75 years, an ECOG performance status 0-1, and adequate organ functions. From January 2011 to February 2016, 152 patients, all with oropharyngeal tumors were enrolled, 77 in arm A and 75 in arm B. Two patients, one in each group, withdrew their consent after randomization, leaving 150 patients for the ITT analysis. PFS at 2 years was 84.2% (95% CI 76.4-92.8) in arm A and 78.4% (95% CI 69.5-88.3) in arm B (HR 1.39, 95% CI 0.69-2.79, p = 0.40). At the time of analysis, there were 26 disease failures, 9 in arm A and 17 in arm B. In arm A, 3 patients had local, 2 regional, and 4 distant relapses as first sites of recurrence, and in arm B, 4, 4, and 9 relapses in corresponding sites. Eight out of 26 patients with disease progression had salvage therapy and 7 were alive NED (no evidence of disease), at 2 years. Locoregional control was 96% in arm A and 97.3% in arm B and OS 93% and 90.5%, respectively. Local failure as first site of recurrence was low, in 4.6% of patients and was similar for T1/T2 and T3/T4 tumors (n.s). Nevertheless, out of 7 patients with primary local failures, 4 were treated with the escalated RT dose. Toxicity was low and similar in the treatment arms. There was one fatal event in arm A where the combined effects of the drugs used in chemotherapy and cetuximab could not be ruled out. PFS, locoregional control and toxicity did not differ between the two arms, OS was high, and there were few local relapses. In arm B, more than twice as many patients had distant metastasis as the first site of relapse compared to arm A. The response to IC was found to define 29% of patients in arm A who did not have a tumor relapse during follow-up. An escalated dose of 74.8 Gy could mitigate the negative impact of large tumor volume but for some patients, even this intensified treatment was insufficient.

Towards transcervical ultrasound image guidance for transoral robotic surgery.

Trans-oral robotic surgery (TORS) using the da Vinci surgical robot is a new minimally-invasive surgery method to treat oropharyngeal tumors, but it is a challenging operation. Augmented reality (AR) based on intra-operative ultrasound (US) has the potential to enhance the visualization of the anatomy and cancerous tumors to provide additional tools for decision-making in surgery. We propose a US-guided AR system for TORS, with the transducer placed on the neck for a transcervical view. Firstly, we perform a novel MRI-to-transcervical 3D US registration study, comprising (i) preoperative MRI to preoperative US registration, and (ii) preoperative to intraoperative US registration to account for tissue deformation due to retraction. Secondly, we develop a US-robot calibration method with an optical tracker and demonstrate its use in an AR system that displays anatomy models in the surgeon's console in real-time. Our AR system achieves a projection error from the US to the stereo cameras of 27.14 and 26.03 pixels (image is 540[Formula: see text]960) in a water bath experiment. The average target registration error (TRE) for MRI to 3D US is 8.90mm for the 3D US transducer and 5.85mm for freehand 3D US, and the TRE for pre-intra operative US registration is 7.90mm. We demonstrate the feasibility of each component of the first complete pipeline for MRI-US-robot-patient registration for a proof-of-concept transcervical US-guided AR system for TORS. Our results show that trans-cervical 3D US is a promising technique for TORS image guidance.

CDKN2A/p16 evaluation in cytology specimens.

CDKN2A/p16 evaluation in cytology specimens.

Supportive Care Needs Among Head and Neck Cancer Patients Prior to Oncologic Treatment: A Prospective, Nested Cross-Sectional Qualitative Analysis.

To qualitatively characterize pretreatment head and neck cancer (HNC) patients' supportive care (SC) needs, attitudes toward SC, and barriers to SC utilization. A prospective, nested, bi-institutional, cross-sectional pilot study design was employed. Participants were sub-selected from a representative sample of 50 patients newly diagnosed with mucosal or salivary gland HNC or sarcoma of the head and neck. Eligibility criteria included reporting ≥2 unmet needs (according to the Supportive Care Needs Survey-Short Form 34) or clinically-significant distress (National Comprehensive Cancer Network Distress Thermometer score ≥4). Semi-structured interviews were performed prior to initiation of oncologic treatment. Audio-recorded interviews were transcribed and thematically analyzed using NVivo 12.0 (QSR Australia). Thematic findings and representative quotes were interpreted by the entire research team. Twenty-seven patients were interviewed. One-third were treated at the county safety-net hospital and the remainder were treated at the university health system. An equal proportion of patients presented with oral cavity, oropharyngeal, and laryngeal or other tumors. Two significant findings were identified on semi-structured interviews. First, patients did not perceive the relevance of SC prior to treatment. Second, anxiety surrounding the HNC diagnosis and impending treatment dominated in the pretreatment phase. Improved HNC patient education about the relevance and importance of SC in the pretreatment setting is needed. Integration of social work or psychological services in HNC clinics is warranted to address patients' cancer-related worry-a discrete, dominant pretreatment SC need.