The Relationships Between Radiation Dosage and Long-term Swallowing Kinematics and Timing in Nasopharyngeal Carcinoma Survivors.

This study aimed to investigate the relationship between intensity-modulated radiation therapy (IMRT) dosimetry and swallowing kinematic and timing measures. Thirteen kinematic and timing measures of swallowing from videofluoroscopic analysis were used as outcome measures to reflect swallowing function. IMRT dosimetry was accessed for thirteen swallowing-related structures. A cohort of 44 nasopharyngeal carcinoma (NPC) survivors at least 3 years post-IMRT were recruited. The cohort had a mean age of 53.2 ± 11.9 years, 77.3% of whom were male. There was an average of 68.24 ± 14.15 months since end of IMRT; 41 (93.2%) had undergone concurrent chemotherapy. For displacement measures, female sex and higher doses to the cricopharyngeus, glottic larynx, and base of tongue were associated with reduced hyolaryngeal excursion and pharyngeal constriction, and more residue. For timing measures, higher dose to the genioglossus was associated with reduced processing time at all stages of the swallow. The inferior pharyngeal constrictor emerged with a distinctly different pattern of association with mean radiation dosage compared to other structures. Greater changes to swallowing kinematics and timing were observed for pudding thick consistency than thin liquid. Increasing radiation dosage to swallowing-related structures is associated with reduced swallowing kinematics. However, not all structures are affected the same way, therefore organ sparing during treatment planning for IMRT needs to consider function rather than focusing on select muscles. Dose-response relationships should be investigated with a comprehensive set of swallowing structures to capture the holistic process of swallowing.

High-risk human papillomavirus positive primary squamous cell carcinoma of the lacrimal gland: a case report.

A 78-year-old Caucasian female presented with a painless mass in the right orbit that had progressively enlarged over several months. Computed tomography scan of the orbits showed a right lacrimal gland mass with no bony erosion. Histopathologic analysis of the biopsy specimen revealed invasive squamous cell carcinoma positive via in-situ hybridization for high-risk human papillomavirus. The patient underwent successful removal of the right lacrimal gland tumor en bloc, followed by adjuvant radiotherapy. This is an extremely rare case of primary squamous cell carcinoma of the lacrimal gland and the first report describing human papillomavirus positivity in this tumor location.

De-intensified adjuvant (chemo)radiotherapy versus standard adjuvant chemoradiotherapy post transoral minimally invasive surgery for resectable HPV-positive oropharyngeal carcinoma.

BACKGROUND: More than 400,000 cases of oropharyngeal squamous cell cancer (OPSCC) are diagnosed every year worldwide and this is rising. Much of the increase has been attributed to human papillomavirus (HPV). HPV-positive OPSCC patients are often younger and have significantly improved survival relative to HPV-negative patients. Traditional management of OPSCC has been with radiotherapy with or without chemotherapy, as this was shown to have similar survival to open surgery but with significantly lower morbidity. Techniques have evolved, however, with the development of computerised planning and intensity-modulated radiotherapy, and of minimally invasive surgical techniques. Acute and late toxicities associated with chemoradiotherapy are a significant burden for OPSCC patients and with an ever-younger cohort, any strategies that could decrease treatment-associated morbidity should be investigated. OBJECTIVES: To assess the effects of de-intensified adjuvant (chemo)radiotherapy in comparison to standard adjuvant (chemo)radiotherapy in patients treated with minimally invasive transoral surgery (transoral robotic surgery or transoral laser microsurgery) for resectable HPV-positive oropharyngeal squamous cell carcinoma. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 26 April 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with carcinoma of the oropharynx (as defined by the World Health Organization classification C09, C10). Cancers included were primary HPV-positive squamous cell tumours originating from the oropharyngeal mucosa. Tumours were classified as T1-4a with or without nodal spread and with no evidence of distant metastatic spread. The intervention was minimally invasive transoral surgery followed by de-intensified adjuvant therapy (either omission of chemotherapy or reduced-dose radiotherapy). The comparator was minimally invasive transoral surgery followed by standard concurrent chemoradiotherapy or standard-dose radiotherapy. The treatments received were of curative intent and patients had not undergone any prior intervention, other than diagnostic biopsy. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related survival was to be studied where possible) and disease-free survival, measured at one, two, three and five years. Our secondary outcomes included assessment of swallowing ability and voice, measured at one, six, 12 and 24 months. We planned to use GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: We did not identify any completed RCTs that met our inclusion criteria. However, three eligible studies are in progress:ADEPT is a phase III trial comparing postoperative radiotherapy with or without cisplatin in HPV-positive T1-4a OPSCC patients. Included patients must have received minimally invasive surgery and demonstrated extra-capsular spread from disease in the neck.ECOG-E3311 is a phase II trial of treatment for HPV-positive locally advanced OPSCC (stages III-IVa + IVb without distant metastasis). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy.PATHOS is a phase III trial of treatment for HPV-positive OPSCC (T1-3, N0-2b). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy. High-risk patients are randomised to radiotherapy with or without concurrent cisplatin. AUTHORS' CONCLUSIONS: This review highlights the current lack of high-quality randomised controlled trials studying treatment de-escalation after minimally invasive surgery in patients with HPV-positive OPSCC. However, trials that will meet the inclusion criteria for this review are in progress with results expected between 2021 and 2023.

Feasibility of a Mobile Application to Enhance Swallowing Therapy for Patients Undergoing Radiation-Based Treatment for Head and Neck Cancer.

Dysphagia following treatment for head and neck cancer is one of the most significant morbidities impacting quality of life. Despite the value of prophylactic exercises to mitigate the impact of radiation on long-term swallowing function, adherence to treatment is limited. The purpose of this investigation was to explore the feasibility of a mobile health application to support patient adherence to swallowing therapy during radiation-based treatment. 36 patients undergoing radiation therapy were provided with the Vibrent™ mobile application as an adjunct to standard swallowing therapy. The application included exercise videos, written instructions, reminders, exercise logging, and educational content. 80% of participants used the app during treatment and logged an average of 102 exercise sessions over the course of treatment. 25% of participants logged at least two exercise sessions per day over the 7-week treatment period, and 53% recorded at least one session per day. Exit interviews regarding the patient experience with the Vibrent™ mobile application were largely positive, but also provided actionable strategies to improve future versions of the application. The Vibrent™ mobile application appears to be a tool that can be feasibly integrated into existing patient care practices and may assist patients in adhering to treatment recommendations and facilitate communication between patients and providers between encounters.

Data integrity systems for organ contours in radiation therapy planning.

The purpose of this research is to develop effective data integrity models for contoured anatomy in a radiotherapy workflow for both real-time and retrospective analysis. Within this study, two classes of contour integrity models were developed: data driven models and contiguousness models. The data driven models aim to highlight contours which deviate from a gross set of contours from similar disease sites and encompass the following regions of interest (ROI): bladder, femoral heads, spinal cord, and rectum. The contiguousness models, which individually analyze the geometry of contours to detect possible errors, are applied across many different ROI's and are divided into two metrics: Extent and Region Growing over volume. After analysis, we found that 70% of detected bladder contours were verified as suspicious. The spinal cord and rectum models verified that 73% and 80% of contours were suspicious respectively. The contiguousness models were the most accurate models and the Region Growing model was the most accurate submodel. 100% of the detected noncontiguous contours were verified as suspicious, but in the cases of spinal cord, femoral heads, bladder, and rectum, the Region Growing model detected additional two to five suspicious contours that the Extent model failed to detect. When conducting a blind review to detect false negatives, it was found that all the data driven models failed to detect all suspicious contours. The Region Growing contiguousness model produced zero false negatives in all regions of interest other than prostate. With regards to runtime, the contiguousness via extent model took an average of 0.2 s per contour. On the other hand, the region growing method had a longer runtime which was dependent on the number of voxels in the contour. Both contiguousness models have potential for real-time use in clinical radiotherapy while the data driven models are better suited for retrospective use.

Evaluation of proposed staging systems for human papillomavirus-related oropharyngeal squamous cell carcinoma.

BACKGROUND: Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) have improved survival when compared with those with HPV-negative OPC. Unfortunately, the American Joint Committee on Cancer seventh edition (AJCC-7ed) staging system does not account for the prognostic advantage observed with HPV-positive OPC. The purpose of the current study was to validate and compare 2 recently proposed staging systems for HPV-positive OPC. METHODS: Patients treated for HPV-positive OPC from 2005 to 2015 at Johns Hopkins Hospital (JHH) were included for analysis. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) and The University of Texas MD Anderson Cancer Center (MDACC) staging systems were applied and survival was calculated using Kaplan-Meier methods. Cox proportional hazard regression was used to determine the relationship between stage of disease and survival. Models were compared using the Akaike information criterion (AIC). RESULTS: A total of 435 patients were eligible for analysis. There was a dramatic shift in lymph node category and overall stage of disease when ICON-S and MDACC stage were applied to the JHH cohort. There was superior stratification of overall survival and progression-free survival by ICON-S stage. Both proposed models had an improved fit based on AIC scores (P<.001 for both) over the AJCC-7ed. The ICON-S staging system had the lowest AIC score, and thus a better fit within the JHH population. CONCLUSIONS: The current analysis provides external validation for both staging systems in an independent and heterogeneously treated patient population. Although the MDACC staging system is an improvement over the AJCC-7ed, the ICON-S stage provides superior stratification of overall and progression-free survival, thereby supporting its use as the updated AJCC staging system for OPC. Cancer 2017;123:1768-1777. © 2017 American Cancer Society.

Clinical utility of a functional lumen imaging probe in management of dysphagia following head and neck cancer therapies.

Background and aims Chemoradiotherapy for head and neck cancer (HNC) with/without laryngectomy commonly causes dysphagia. Pharyngoesophageal junction (PEJ) stricturing is an important contributor. We aimed to validate a functional lumen imaging probe (the EndoFLIP system) as a tool for quantitating pretreatment PEJ distensibility and treatment-related changes in HNC survivors with dysphagia and to evaluate the diagnostic accuracy of EndoFLIP-derived distensibility in detecting PEJ strictures. Methods We studied 34 consecutive HNC survivors with long-term (> 12 months) dysphagia who underwent endoscopic dilation for suspected strictures. Twenty non-dysphagic patients undergoing routine endoscopy served as controls. PEJ distensibility was measured at endoscopy with the EndoFLIP system pre- and post-dilation. PEJ stricture was defined as the presence of a mucosal tear post-dilation. Results PEJ stricture was confirmed in 22/34 HNC patients (65 %). During distension up to 60 mmHg, the mean EndoFLIP-derived narrowest cross-sectional area (nCSA) in HNC patients with strictures, without strictures, and in controls were 58 mm2 (95 % confidence interval [CI] 22 to 118), 195 mm2 (95 %CI 129 to 334), and 227 mm2 (95 %CI 168 to 316), respectively. A cutoff of 114 mm2 for the nCSA at the PEJ had perfect diagnostic accuracy in detecting strictures (area under the receiver operating characteristic curve = 1). In patients with strictures, a single session of dilation increased the nCSA by 29 mm2 (95 %CI 20 to 37; P < 0.001). In patients with no strictures, dilation caused no change in the nCSA (mean difference 13 mm2 [95 %CI -4 to 30]; P = 0.13). Conclusions EndoFLIP is a highly accurate technique for the detection of PEJ strictures. EndoFLIP may complement conventional diagnostic tools in the detection of pharyngeal outflow obstruction.

Surface markers for guiding cylindrical diffuser fiber insertion in interstitial photodynamic therapy of head and neck cancer.

BACKGROUND AND OBJECTIVES: Image-based treatment planning can be used to compute the delivered light dose during interstitial photodynamic therapy (I-PDT) of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The objectives of this work were to evaluate the use of surface fiducial markers and flexible adhesive grids in guiding interstitial placement of laser fibers, and to quantify the impact of discrepancies in fiber location on the expected light dose volume histograms (DVHs). METHODS: Seven gel-based phantoms were made to mimic geometries of LA-HNSCC. Clinical flexible grids and fiducial markers were used to guide the insertion of optically transparent catheters, which are used to place cylindrical diffuser fibers within the phantoms. A computed tomography (CT) was used to image the markers and phantoms before and after catheter insertion and to determine the difference between the planned and actual location of the catheters. A finite element method was utilized to compute the light DVHs. Statistical analysis was employed to evaluate the accuracy of fiber placement and to investigate the correlation between the location of the fibers and the calculated DVHs. RESULTS: There was a statistically significant difference (P = 0.018) between all seven phantoms in terms of the mean displacement. There was also statistically significant correlation between DVHs and depth of insertion (P = 0.0027), but not with the lateral displacement (P = 0.3043). The maximum difference between actual and planned DVH was related to the number of fibers (P = 0.0025) and the treatment time. CONCLUSIONS: Surface markers and a flexible grid can be used to assist in the administration of a prescribed DVH within 15% of the target dose provided that the treatment fibers are placed within 1.3 cm of the planned depth of insertion in anatomies mimicking LA-HNSCC. The results suggest that the number of cylindrical diffuser fibers and treatment time can impact the delivered DVHs. Lasers Surg. Med. 49:599-608, 2017. © 2017 Wiley Periodicals, Inc.

One-Year Swallowing Outcomes in Patients Treated with Prophylactic Gabapentin During Radiation-Based Treatment for Oropharyngeal Cancer.

Recent investigations by our study team have demonstrated patients using gabapentin for pain management during chemoradiotherapy (CRT) do well maintaining swallowing during treatment with less need for narcotic pain medication, PEG dependence, weight loss, and short-term swallowing morbidity. The purpose of this investigation was to characterize the long-term swallowing function of these patients 1-year following treatment. Sequential patients receiving CRT for oropharyngeal cancer and concurrent gabapentin were evaluated 1-year following treatment for swallowing outcomes. Functional Oral Intake Scores (FOIS) were utilized to assess diet level. The MD Anderson Dysphagia Inventory (MDADI) was chosen to evaluate patient perception of swallowing function. Videofluoroscopic swallowing studies were completed approximately 1 year after treatment to assess physiologic outcomes as well as Penetration Aspiration Scores (PAS). Data from 26 consecutive participants were available for analysis. The majority of patients had advanced stage disease (Stage 3-4). No patients had a PEG tube 1-year following treatment, and the mean FOIS score was 6.83. Pharyngeal deficits were infrequent with reduced pharyngeal constriction and prominence/early closure of cricopharyngeus predominating. Mean PAS score was 1.5, indicating that the majority of patients had either no laryngeal penetration/aspiration, or transient penetration that was fully cleared. Mean MDADI score was 85.52, indicating that, in general, patients perceived their swallowing to be minimally impaired. Patients receiving gabapentin pain management as part of a comprehensive dysphagia prevention protocol during CRT have excellent long-term swallowing outcomes as reflected in diet levels, physiologic functioning, and patient-perceived quality of life.

Predictive Factors for Prophylactic Percutaneous Endoscopic Gastrostomy (PEG) Tube Placement and Use in Head and Neck Patients Following Intensity-Modulated Radiation Therapy (IMRT) Treatment: Concordance, Discrepancies, and the Role of Gabapentin.

The prophylactic placement of a percutaneous endoscopic gastrostomy (PEG) tube in the head and neck cancer (HNC) patient is controversial. We sought to identify factors associated with prophylactic PEG placement and actual PEG use. Since 2010, data regarding PEG placement and use were prospectively recorded in a departmental database from January 2010 to December 2012. HNC patients treated with intensity-modulated radiation therapy (IMRT) were retrospectively evaluated from 2010 to 2012. Variables potentially associated with patient post-radiation dysphagia from previous literature, and our experience was evaluated. We performed multivariate logistic regression on these variables with PEG placement and PEG use, respectively, to compare the difference of association between the two arms. We identified 192 HNC patients treated with IMRT. Prophylactic PEG placement occurred in 121 (63.0 %) patients, with PEG use in 97 (80.2 %) patients. PEG placement was associated with male gender (p < .01), N stage ≥ N2 (p < .05), pretreatment swallowing difficulties (p < .01), concurrent chemotherapy (p < .01), pretreatment KPS ≥80 (p = .01), and previous surgery (p = .02). Concurrent chemotherapy (p = .03) was positively associated with the use of PEG feeding by the patient, whereas pretreatment KPS ≥80 (p = .03) and prophylactic gabapentin use (p < .01) were negatively associated with PEG use. The analysis suggests there were discrepancies between prophylactic PEG tube placement and actual use. Favorable pretreatment KPS, no pretreatment dysphagia, no concurrent chemotherapy, and the use of gabapentin were significantly associated with reduced PEG use. This analysis may help refine the indications for prophylactic PEG placement.

The Effect of Radiation Dose on Swallowing: Evaluation of Aspiration and Kinematics.

Radiation oncologists have focused on the pharyngeal constrictors as the primary muscles of concern for dysphagia. However, our prior investigations have demonstrated that radiation dose to the geniohyoid rather than the constrictor muscles was more closely related to penetration aspiration scores (PAS). We examined the relationship between (1) radiation dose and swallowing temporal kinematics, and (2) between PAS and swallowing kinematics in these patients. Videofluoroscopic swallowing studies of 41 patients following radiation therapy for oropharyngeal cancer were analyzed for thin liquid boluses. Timing measures included duration of laryngeal vestibule closure (DLVC), duration to maximum hyoid elevation (DTMHE), duration to cricopharyngeal opening (DTCPO), and pharyngeal transit time (PTT). PAS was extracted for each swallow and considered normal if ≤ 2. As minimum and mean dose to the geniohyoid increased, DTMHE, DTCPO, and PTT increased. Worse PA scores were most strongly correlated with radiation dose received by geniohyoid (r = 0.445, p < 0.0001). Mean DLVC varied according to PAS group (normal PAS mean = 0.67 s, abnormal PAS mean = 0.13 s; p < 0.001). Similarly, DTCPO was significantly different based upon PAS (normal PAS mean = 0.22 s, abnormal PAS mean = 0.37 s, p = 0.016). As PAS increased, DTPCO and PTT increased (r = 0.208, p = 0.04; r = 0.204, p = 0.043). A negative correlation was noted between PAS and DLVC (r = -0.375, p = 0.001). Higher doses of radiation to the geniohyoid muscles are associated with increased severity of dysphagia as measured through both kinematics and PAS. Consideration of dose to the geniohyoid should be considered when planning radiation.

FDG volumetric parameters and survival outcomes after definitive chemoradiotherapy in patients with recurrent head and neck squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to establish the predictive value of (18)F-FDG parameters for overall survival in biopsy-proven recurrent head and neck squamous cell cancer (HNSCC) patients after definitive chemoradiotherapy. MATERIALS AND METHODS: We conducted a retrospective study including 34 patients with HNSCC who had biopsy-proven recurrence between April 2004 and March 2012 and underwent FDG PET/CT at our institution at the time of recurrence. Maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. The primary outcome measure was overall survival. ROC analysis, univariate and multivariate Cox regression models, and Kaplan-Meir survival curves were performed. RESULTS: In univariate analyses, human papillomavirus (HPV) status (p = 0.04), primary site recurrence of MTV (p = 0.03), metastasis of MTV (p = 0.02), metastasis of TLG (p = 0.02), total MTV (p = 0.002), and total TLG (p = 0.04) were significantly associated with overall survival outcome. Total MTV remained as significant independent prognostic factor when adjusted for all other covariates except for primary site recurrence SUVmax and SUVpeak and lymph node SUVmax and SUVpeak. There was a significant difference in time to survival between patients with total MTV above and below the 50th percentile (Mantel-Cox log-rank test, p = 0.05 and Gehan-Breslow-Wilcoxon test, p = 0.03) and the optimum threshold of 16.8 mL (Mantel-Cox log-rank test, p = 0.01 and Gehan-Breslow-Wilcoxon test, p = 0.01; hazard ratio [HR], 0.25). CONCLUSION: FDG PET/CT-based total MTV and clinical HPV status may be significant prognostic markers for overall survival of patients with recurrent HNSCC after definitive chemoradiotherapy.

Effect of gabapentin on swallowing during and after chemoradiation for oropharyngeal squamous cell cancer.

The aim of this study was to examine the impact of gabapentin (neurontin) on swallowing and feeding tube use during chemoradiation (CRT) for oropharyngeal squamous cell carcinoma (OPSCC), and physiologic swallowing outcomes following completion of treatment. A total of 23 patients treated for OPSCC with concurrent CRT and prophylactically treated for pain using gabapentin were assessed. Historical controls were matched for T stage and primary site of disease. Timing of PEG use and removal were recorded. Video fluoroscopic swallowing studies were completed post-treatment to assess physiologic outcomes as well as penetration-aspiration scores (PAS). Functional oral intake scale (FOIS) scores were determined at the time of swallowing evaluation to assess diet level. Patients treated with gabapentin began using their PEG tubes later (3.7 vs. 2.29 weeks; P = 0.013) and had their PEG tubes removed earlier (7.29 vs. 32.56 weeks; P = 0.039) than the historical controls. A number of physiologic parameters were found to be less impacted in the gabapentin group, including oral bolus control (P = 0.01), epiglottic tilt (P = 0.0007), laryngeal elevation (P = 0.0017), and pharyngeal constriction (P = 0.002). PAS scores were significantly lower in the group treated with gabapentin (1.89 vs. 4; P = 0.0052). Patients receiving gabapentin had more advanced diet levels at the time of the initial swallowing study as evidenced by their FOIS scores (5.4 vs. 3.21; P = 0.0003). We conclude that patients using gabapentin for pain management during CRT appears to do well maintaining swallow function during treatment and have favorable post-treatment physiologic swallowing outcomes. Prospective evaluation is warranted.

Increasing radiation therapy and lower survival for human papillomavirus-related oropharynx cancer associated with a shift to community cancer center care.

BACKGROUND: Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment. METHODS: This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers. RESULTS: The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P < .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P < .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34). CONCLUSIONS: Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival.

Radiation immunodynamics in patients with glioblastoma receiving chemoradiation.

Introduction: This is a prospective, rigorous inquiry into the systemic immune effects of standard adjuvant chemoradiotherapy, for WHO grade 4, glioblastoma. The purpose is to identify peripheral immunologic effects never yet reported in key immune populations, including myeloid-derived suppressor cells, which are critical to the immune suppressive environment of glioblastoma. We hypothesize that harmful immune-supportive white blood cells, myeloid derived suppressor cells, expand in response to conventionally fractionated radiotherapy with concurrent temozolomide, essentially promoting systemic immunity similar what is seen in chronic diseases like diabetes and heart disease. Methods: 16 patients were enrolled in a single-institution, observational, immune surveillance study where peripheral blood was collected and interrogated by flow cytometry and RNAseq. Tumor tissue from baseline assessment was analyzed with spatial proteomics to link peripheral blood findings to baseline tissue characteristics. Results: We identified an increase in myeloid-derived suppressor cells during the final week of a six-week treatment of chemoradiotherapy in peripheral blood of patients that were not alive at two years after diagnosis compared to those who were living. This was also associated with a decrease in CD8+ T lymphocytes that produced IFNγ, the potent anti-tumor cytokine. Discussion: These data suggest that, as in chronic inflammatory disease, systemic immunity is impaired following delivery of adjuvant chemoradiotherapy. Finally, baseline investigation of myeloid cells within tumor tissue did not differ between survival groups, indicating immune surveillance of peripheral blood during adjuvant therapy may be a critical missing link to educate our understanding of the immune effects of standard of care therapy for glioblastoma.

Lower survival for surgical treatment of HPV-related oropharynx cancer at community cancer centers.

BACKGROUND: The rate of primary surgery for human papillomavirus-related oropharynx cancer (HPVOPC) has recently declined, while utilization of transoral robotic surgery (TORS) has lagged at community cancer centers (CCs). We hypothesize that differences in overall survival (OS) exist between patients undergoing surgery for HPVOPC at CCs and low (<15 TORS/year; LVACs) and high (≥15 TORS/year; HVACS) TORS volume academic centers. METHODS: Cases from the US National Cancer Database with a diagnosis of HPVOPC from 2010-2019 that underwent primary surgical treatment were included. Trends in TORS utilization, rates of positive surgical margins (PMs), quality of adjuvant treatment and 5-year OS were compared between CCs, LVACs and HVACs. RESULTS: 5,406 cases met study criteria. A significantly lower proportion of cases at CCs utilized TORS than at LVACs or HVACs (26.2% vs 44.0% vs 73.9%, respectively, p < .001). The rate of PMs was significantly higher at CCs than at LVACs or HVACs (25.7% vs 15.3% vs 9.2%, p < .001). A greater proportion of cases undergoing adjuvant radiotherapy (RT) received prolonged courses (23.6% vs 13.1% vs 8.8%, p < .001) or excessive doses (16.5% vs 11.5% vs 8.7%, p < .001) of RT at CCs than at LVACs or HVACs, respectively. 5-year OS was lowest at CCs (85.2%, 95%CI: 81.7-88.2%), intermediate at LVACs (88.9%, 95%CI: 87.2-90.4%), and highest at HVACs (91.4%, 95%CI: 89.5-92.9%; pLR<0.01). CONCLUSIONS: Significant differences in the type and quality of surgical and adjuvant treatment for HPVOPC exist between facility types based on TORS volume. Overall survival was lowest at CCs, intermediate at LVACs and highest at HVACs.

Proposal for standardized ultrasound analysis of the salivary glands: Part 1 submandibular gland.

Objectives: The Salivary Gland Committee of the American Academy of Otolaryngology-Head and Neck Surgery seeks to standardize terminology and technique for ultrasonograpy used in the evaluation and treatment of salivary gland disorders. Methods: Development of expert opinion obtained through interaction with international practitioners representing multiple specialties. This committee work includes a comprehensive literature review with presentation of case examples to propose a standardized protocol for the language used in ultrasound salivary gland assessment. Results: A multiple segment proposal is initiated with this focus on the submandibular gland. We provide a concise rationale for recommended descriptive language highlighted by a more extensive supplement that includes an extensive literature review with additional case examples. Conclusion: Recommendations are provided to improve consistency both in performing and reporting submandibular gland ultrasound.

Pretreatment diffusion-weighted and dynamic contrast-enhanced MRI for prediction of local treatment response in squamous cell carcinomas of the head and neck.

OBJECTIVE: The objective of our study was to predict response to chemoradiation therapy in patients with head and neck squamous cell carcinoma (HNSCC) by combined use of diffusion-weighted imaging (DWI) and high-spatial-resolution, high-temporal-resolution dynamic contrast-enhanced MRI (DCE-MRI) parameters from primary tumors and metastatic nodes. SUBJECTS AND METHODS: Thirty-two patients underwent pretreatment DWI and DCE-MRI using a modified radial imaging sequence. Postprocessing of data included motion-correction algorithms to reduce motion artifacts. The median apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), extracellular extravascular volume fraction (v(e)), and plasma volume fraction (v(p)) were computed from primary tumors and nodal masses. The quality of the DCE-MRI maps was estimated using a threshold median chi-square value of 0.10 or less. Multivariate logistic regression and receiver operating characteristic curve analyses were used to determine the best model to discriminate responders from nonresponders. RESULTS: Acceptable χ(2) values were observed from 84% of primary tumors and 100% of nodal masses. Five patients with unsatisfactory DCE-MRI data were excluded and DCE-MRI data for three patients who died of unrelated causes were censored from analysis. The median follow-up for the remaining patients (n = 24) was 23.72 months. When ADC and DCE-MRI parameters (K(trans), v(e), v(p)) from both primary tumors and nodal masses were incorporated into multivariate logistic regression analyses, a considerably higher discriminative accuracy (area under the curve [AUC] = 0.85) with a sensitivity of 81.3% and specificity of 75% was observed in differentiating responders (n = 16) from nonresponders (n = 8). CONCLUSION: The combined use of DWI and DCE-MRI parameters from both primary tumors and nodal masses may aid in prediction of response to chemoradiation therapy in patients with HNSCC.

Close Margins After Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Carcinoma: A Review of the Literature and Practical Recommendations.

The purpose of this article is to summarize the literature and practical recommendations from experienced centers for close margins after transoral robotic surgery for human papillomavirus-positive oropharyngeal carcinoma.

Daily Head and Neck Treatment Assessment for Optimal Proton Therapy Planning Robustness.

Robust optimization in proton therapy ensures adequate target coverage; however, validation of fractional plan quality and setup uncertainty in patients has not been performed. We aimed to assess plan robustness on delivered head and neck proton plans classified into two categories: (1) primary only (PO) and (2) primary and neck nodal (PNN) coverage. Registration at the machine was utilized for daily CBCT to generate a synthetic CT. The dose for the clinical target volume (CTV) and organs at risk (OAR) was compared to the expected robustness bands using 3.5% range uncertainty and 3 mm vs. 5 mm setup uncertainty. The fractional deviation was defined as D95% and V100% outside of uncertainty constraints. About 203 daily fractions from 6 patients were included for analysis. The percentage of fractions that exceeded robustness calculations was greater in 3 mm as compared to 5 mm setup uncertainty for both CTV and OAR volumes. PO plans had clinically insignificant average fractional deviation, less than 1%, in delivered D95% and V100%. In comparison, PNN plans had up to 2.2% average fractional deviation in delivered V100% using 3 mm robustness. Given the need to balance dose accuracy with OAR sparing, we recommend the utilization of 3 mm setup uncertainty as an acceptable simulation of the dose delivered.