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.

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.

Developing the POTOMAC Model: A Novel Prediction Model to Study the Impact of Lymphopenia Kinetics on Survival Outcomes in Head and Neck Cancer Via an Ensemble Tree-Based Machine Learning Approach.

PURPOSE: Lymphopenia is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC), yet there is no consensus on whether we should limit lymphopenia risks during treatment. To fully elucidate the prognostic role of baseline versus treatment-related lymphopenia, a robust analysis is necessary to investigate the relative importance of various lymphopenia metrics (LMs) in predicting survival outcomes. METHODS: In this prospective cohort study, 363 patients were eligible for analysis (patients with newly diagnosed, nonmetastatic HNSCC treated with neck radiation with or without chemotherapy in 2015-2019). Data were acquired on 28 covariates: seven baseline, five disease, seven treatment, and nine LMs, including static and time-varying features for absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio, and immature granulocytes (IGs). IGs were included, given their hypothesized role in inhibiting lymphocyte function. Overall, there were 4.0% missing data. Median follow-up was 2.9 years. We developed a model (POTOMAC) to predict survival outcomes using a random survival forest (RSF) procedure. RSF uses an ensemble approach to reduce the risk of overfitting and provides internal validation of the model using data that are not used in model development. The ability to predict survival risk was assessed using the AUC for the predicted risk score. RESULTS: POTOMAC predicted 2-year survival with AUCs at 0.78 for overall survival (primary end point) and 0.73 for progression-free survival (secondary end point). Top modifiable risk factors included radiation dose and max ALC decrease. Top baseline risk factors included age, Charlson Comorbidity Index, Karnofsky Performance Score, and baseline IGs. Top-ranking LMs had superior prognostic performance when compared with human papillomavirus status, chemotherapy type, and dose (up to 2, 8, and 65 times higher in variable importance score). CONCLUSION: POTOMAC provides important insights into potential approaches to reduce mortality in patients with HNSCC treated by chemoradiation but needs to be validated in future studies.

Development and Testing of a Mobile App to Collect Social Determinants of Health Data in Cancer Settings: Interview Study.

BACKGROUND: Social determinants of health (SDOH) such as lack of basic resources, housing, transportation, and social isolation play an important role for patients on the cancer care continuum. Health systems' current technological solutions for identifying and managing patients' SDOH data largely focus on information recorded in the electronic health record by providers, which is often inaccessible to patients to contribute to or modify. OBJECTIVE: We developed and tested a patient-centric SDOH screening tool designed for use on patients' personal mobile phone that preserves patient privacy and confidentiality, collects information about the unmet social needs of patients with cancer, and communicates them to the provider. METHODS: We interviewed 22 patients with cancer, oncologists, and social workers associated with a US-based comprehensive cancer center to better understand how patients' SDOH information is collected and reported. After triangulating data obtained from thematic analysis of interviews, an environmental scan, and a literature search of validated tools to collect SDOH data, we developed an SDOH screening tool mobile app and conducted a pilot study of 16 dyadic pairs of patients and cancer care team members at the same cancer center. We collected patient SDOH data using 36 survey items covering 7 SDOH domains and used validated scales and follow-up interviews to assess the app's usability and acceptability among patients and cancer care team members. RESULTS: Formative interviews with patients and care team members revealed that transportation, financial challenges, food insecurity, and low health literacy were common SDOH challenges and that a mobile app that collected those data, shared those data with care team members, and offered supportive resources could be useful and valuable. In the pilot study, 25% (4/16) of app-using patients reported having at least one of the abovementioned social needs; the most common social need was social isolation (7/16, 44%). Patients rated the mobile app as easy to use, accurately capturing their SDOH, and preserving their privacy but suggested that the app could be more helpful by connecting patients to actual resources. Providers reported high acceptability and usability of the app. CONCLUSIONS: Use of a brief, patient-centric, mobile app-based SDOH screening tool can effectively capture SDOH of patients with cancer for care team members in a way that preserves patient privacy and that is acceptable and usable for patients and care team members. However, only collecting SDOH information is not sufficient; usefulness can be increased by connecting patients directly to resources to address their unmet social needs.

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.

Smart Radiotherapy Biomaterials for Image-Guided In Situ Cancer Vaccination.

Recent studies have highlighted the potential of smart radiotherapy biomaterials (SRBs) for combining radiotherapy and immunotherapy. These SRBs include smart fiducial markers and smart nanoparticles made with high atomic number materials that can provide requisite image contrast during radiotherapy, increase tumor immunogenicity, and provide sustained local delivery of immunotherapy. Here, we review the state-of-the-art in this area of research, the challenges and opportunities, with a focus on in situ vaccination to expand the role of radiotherapy in the treatment of both local and metastatic disease. A roadmap for clinical translation is outlined with a focus on specific cancers where such an approach is readily translatable or will have the highest impact. The potential of FLASH radiotherapy to synergize with SRBs is discussed including prospects for using SRBs in place of currently used inert radiotherapy biomaterials such as fiducial markers, or spacers. While the bulk of this review focuses on the last decade, in some cases, relevant foundational work extends as far back as the last two and half decades.

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.

Predictors of Free Flap Volume Loss in Nonosseous Reconstruction of Head and Neck Oncologic Defects.

OBJECTIVES: Free tissue reconstruction of the head and neck must be initially overcorrected due to expected postoperative free flap volume loss, which can be accelerated by adjuvant radiation therapy. In this study, we aim to identify patient and treatment-specific factors that may significantly contribute to this phenomenon and translate these characteristics into a predictive model for expected percent free flap volume loss in a given patient. METHODS: Patients with a history of oral cavity and/or oropharyngeal cancer who underwent nonosseous free flap reconstruction were reviewed between January 2009 and November 2018 at a tertiary care center. Demographics/characteristics, total radiation dose, radiation fractionation (RF), and pre/postradiation free flap volume as evaluated by computed tomography imaging were collected. Free flap volume was measured by a fellowship-trained neuroradiologist in all cases. Only patients receiving adjuvant radiotherapy with available pre/postradiation imaging were included. Multivariable linear regression modeling for prediction of free flap volume loss was performed with optimization via stepwise elimination. RESULTS: Thirty patients were included for analysis. Mean flap volume loss was 42.7% ± 17.4%. The model predicted flap volume loss in a significant fashion (P = .004, R2 = 0.49) with a mean magnitude of error of 9.8% ± 7.5%. Age (ß = 0.01, P = .003) and RF (ß = -0.01, P = .009) were individual predictors of flap volume loss. CONCLUSIONS: Our model predicts percent free flap volume loss in a significant fashion. Age and RF are individual predictors of free flap volume loss, the latter being a novel finding that is also modifiable through hyperfractionation radiotherapy schedules.

Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311).

PURPOSE: Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS: E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS: Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION: Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.

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.

Preventing collateral damage.

In pigs, nitrate supplements can protect salivary glands from the damage caused by radiation therapy to the head and neck.

Radiation Therapy After Surgical Resection Improves Outcomes for Patients With Recurrent Pleomorphic Adenoma.

PURPOSE: Pleomorphic adenoma is a benign salivary tumor that may recur multifocally. In case series, the benefit of radiation therapy (RT) for recurrent pleomorphic adenoma remains unclear. We hypothesized that the combination of surgery and adjuvant RT reduces risk of subsequent recurrence compared with surgery alone for recurrent pleomorphic adenoma. METHODS AND MATERIALS: Patients who received diagnoses of recurrent pleomorphic adenoma between 1980 and 2016 were identified using an institutional pathology database. Medical records were retrospectively reviewed to determine clinical, operative, pathologic, and imaging characteristics. Kaplan-Meier methods were used to estimate local control after surgery, stratified by completeness of resection and receipt of adjuvant RT. The association of variables with risk of subsequent local recurrence was analyzed using Cox proportional hazards model, and variance estimates were calculated to account for multiple recurrences in the same patient. Toxicities were prospectively recorded in a departmental database. RESULTS: A total of 49 patients presented with at least 1 recurrence, of which 28 were managed with surgery alone, and 21 were treated with surgery and RT. The median follow-up time after the initial recurrence was 48 months (range, 6-531 months). There were 35 subsequent recurrences; 34 after surgery alone and only 1 after surgery with RT. On multivariate analysis, adjuvant RT was associated with decreased risk of recurrence (hazard ratio, 0.09; 95% confidence interval, 0.02-0.41, P = .002), whereas increasing number of prior recurrences was associated with increased risk (hazard ratio, 1.23; 95% confidence interval, 1.13-1.35, P < .001). Common toxicities of RT included dermatitis, xerostomia, and mucositis. CONCLUSIONS: For patients with recurrent pleomorphic adenoma, the addition of adjuvant RT after surgery is associated with a significant decrease in risk of subsequent tumor recurrence.

Radiation-Induced Skin Dermatitis: Treatment With CamWell® Herb to Soothe® Cream in Patients With Head and Neck Cancer Receiving Radiation Therapy.

BACKGROUND: Radiation-induced skin dermatitis (RISD) is a common outcome experienced by adult patients with head and neck cancer (HNC) who have undergone radiation therapy. There is no standardized recommended agent for the prevention or management of RISD. OBJECTIVES: The primary objective of this study was to retrospectively evaluate for effectiveness of a botanical topical agent, CamWell® Herb to Soothe® cream, on RISD. METHODS: 112 patients with HNC undergoing radiation therapy self-reported their RISD topical skin care agent during treatment as standard of care, CamWell used prophylactically, or CamWell use started after the first week of treatment. The primary endpoint was impact of RISD on the patient, as measured by mean Skindex-16 score throughout treatment. Measures were completed weekly. FINDINGS: The mean Skindex score was statistically significantly lower for the prophylactic group than for the standard-of-care group. CamWell may have played a role in managing RISD when compared to standard-of-care agents.

Bone density and fracture risk following SBRT for non-spine bone metastases.

PURPOSE/METHODS: This retrospective study evaluated local recurrence (LR) and fracture risk in non-spine bone metastases treated with SBRT. RESULTS: 181 lesions in 116 patients are reported. The median dose was 27 Gy (range 15-40) in 3 fractions (range 1-6). The cumulative incidence of LR was 2.8%, 7.2% and 12.5% at 6 mo, 1 yr and 2 yrs. Fractures occurred in 11 lesions (6%). Radioresistant histology and increasing PTV predicted for LR on univariate analysis, while rib location was associated with control. Increasing PTV remained a significant predictor for LR on multivariate analysis. Univariate predictors of fracture risk included female gender, lytic lesions and poorer KPS. Average CT-approximated L1 trabecular attenuation in patients with fracture was significantly lower than in patients without fracture (112.2 vs. 142.6 Hounsfield units). CONCLUSION: In the largest series to date, we report excellent local control for SBRT to non-spine bone metastases and a novel relationship between CT-based bone quality assessment and fracture risk.

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.