Effect of distance of treatment center on survival for HPV-negative head and neck cancer patients.

BACKGROUND: In rural states, travel burden for complex cancer care required for head and neck squamous cell carcinoma (HNSCC) may affect patient survival, but its impact is unknown. METHODS: Patients with HPV-negative HNSCC were retrospectively identified from a statewide, population-based study. Euclidian distance from the home address to the treatment center was calculated for radiation therapy, surgery, and chemotherapy. Multivariable Cox proportional hazards models were used to examine the risk of 5-year mortality with increasing travel quartiles. RESULTS: There were 936 patients with HPV-negative HNSCC with a mean age of 60. Patients traveled a median distance of 10.2, 11.1, and 10.9 miles to receive radiation therapy, surgery, and chemotherapy, respectively. Patients in the fourth distance quartile were more likely to live in a rural location (p < 0.001) and receive treatment at an academic hospital (p < 0.001). Adjusted overall survival (OS) improved proportionally to distance traveled, with improved OS remaining significant for patients who traveled the furthest for care (third and fourth quartile by distance). Relative to patients in the first quartile, patients in the fourth had a reduced risk of mortality with radiation (HR 0.59, 95% CI 0.42-0.83; p = 0.002), surgery (HR 0.47, 95% CI 0.30-0.75; p = 0.001), and chemotherapy (HR 0.56, 95% CI 0.35-0.91; p = 0.020). CONCLUSION: For patients in this population-based cohort, those traveling greater distances for treatment of HPV-negative HNSCC had improved OS. This analysis suggests that the benefits of coordinated, multidisciplinary care may outweigh the barriers of travel burden for these patients.

A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established. METHODS: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC. The primary end point was a hypothesized pathologic complete response rate of 50%. After chemo-immunotherapy and surgical resection, patients received study-defined, pathologic risk adapted adjuvant therapy consisting of either durvalumab alone (low risk), involved field radiation plus weekly cisplatin and durvalumab (intermediate risk), or standard chemoradiation plus durvalumab (high risk). RESULTS: Between December 2017 and November 2021, 39 subjects were enrolled at three centers. Oral cavity was the most common primary site (69%). A total of 35 of 39 subjects underwent planned surgical resection; one subject had a delay in surgery due to treatment-related toxicity. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. Post treatment imaging demonstrated an objective response rate of 57%. Pathologic complete response and major pathologic response were achieved in 29% and 49% of subjects who underwent planned surgery, respectively. The 1-year progression-free survival was 83.8% (95% confidence interval, 67.4%-92.4%). CONCLUSIONS: Neoadjuvant carboplatin, nab-paclitaxel, and durvalumab before surgical resection of HNSCC were safe and feasible. Although the primary end point was not met, encouraging rates of pathologic complete response and clinical to pathologic downstaging were observed.

Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction.

OBJECTIVES: Bone resorption of more conventional vascularized bone grafts have been well described showing minimal resorption over time. Few studies have evaluated osseous union and bone resorption in scapula tip free flaps (STFF) in the reconstruction of mandibulectomy defects. We aimed to describe our series on STFF with respect to osseous union and bone resorption over time. METHODS: Retrospective chart review of patients receiving STFF from January 2014-January 2017 (n = 25). A neuroradiologist analyzed follow-up CT scans to assess (1) STFF complete, partial, or no osseous union with native mandible and (2) STFF volume change over time in a subset with multiple follow-up scans (n = 18). RESULTS: Twenty-three of 25 patients (92%) showed complete or partial STFF osseous union with native mandible either distally or proximally. STFF volume change ranged from +4.8 to -54% (median -0.5%) over median follow-up interval of 23 months. History of chemoradiation therapy, bisphophonate use, sex, age, or smoking history did not correlate with bone resorption. CONCLUSIONS: STFFs shows high rates of osseous union and limited bone resorption that is equivalent to, or less than, vascularized fibular and iliac crest flaps. Clinically, this translates into both optimal healing and functional and cosmetic outcomes, especially in the setting of prior therapies. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2597-2602, 2023.

Diagnostic accuracy of FNA to determine HPV status in HPV-associated oropharyngeal squamous cell carcinoma.

PURPOSE/OBJECTIVE(S): Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) affects prognosis and can alter the treatment plan. We evaluated the diagnostic accuracy of FNA biopsies to determine malignancy and HPV status in OPSCC at our institution. METHODS: Pathology samples from consecutive patients with pathologically confirmed HPV-associated OPSCC who underwent FNA of a cervical lymph node during initial diagnostic work-up were retrospectively analyzed between November 2015 and August 2021. RESULTS: Initial FNA was diagnostic for malignancy in 109/148 (73.6%) patients and non-diagnostic in 39/148 (26.4%). P16 staining of FNAs positive for malignancy showed: 54/109 (49.5%) p16 positive, 6/109 (5.5%) p16 negative, 49/109 (45.0%) p16 indeterminate. In patients with an initial non-diagnostic sampling or p16 indeterminate, repeat FNA was performed in 30/88 (34.1%) patients. Of the 30 repeat FNAs: 23/30 (76.7%) were diagnostic of malignancy and 7/30 (23.3%) remained non-diagnostic for malignancy. Of the 23 repeat FNAs diagnostic of malignancy: 16/23 (69.6%) were p16 positive and 7/23 (30.4%) were p16 indeterminate. In summary, 88/148 (59.5%) initial FNAs and 14/30 (46.7%) of repeat FNAs were non-diagnostic of malignancy or p16 indeterminate. Final yield of FNA biopsies (initial and first repeat FNA) to diagnose malignancy and p16 status was 70/148 (47.3%). CONCLUSIONS: Fine needle aspirations of lymph nodes in patients with HPV-associated OPSCC are frequently non-diagnostic for malignancy or indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.

Skull Base Regeneration During Treatment With Chemoradiation for Nasopharyngeal Carcinoma: A Case Report.

Background: Advanced cases of nasopharyngal carcinoma can present with skull base invasion. Treatment of these advanced cases with radiotherapy poses a challenge given proximity of tumor to critical neural structures as well as concern that a skull base defect and associated complications could develop with tumor regression. Case Presentation: A 34-year-old male patient presented with a 7-cm nasopharyngeal tumor invading the skull base with destruction of the clivus and intracranial extension. He underwent a course of definitive chemoradiation, requiring use of adaptive radiotherapy, that resulted in complete tumor regression and is free of disease 5 years posttreatment. Imaging done during treatment demonstrated that significant regeneration of bone occurred simultaneously with tumor regression. Conclusions: This case demonstrates that it is possible for bony regeneration to occur simultaneously with tumor regression in a patient with skull base invasion by tumor, precluding the need for neurosurgical intervention.

Evaluation of a 3D-Printed Transoral Robotic Surgery Simulator Utilizing Artificial Tissue.

OBJECTIVES/HYPOTHESIS: Transoral robotic surgery (TORS) poses challenges for operators in training, with limited robot access on a platform requiring distinct surgical skills. Few simulators exist, and current virtual reality training modules exclude head and neck simulations. This study evaluates the construct validity for a novel low-cost TORS simulator. STUDY DESIGN: Single institution prospective observational study. METHODS: Using 3D-printed oral cavity structures and replaceable artificial tissue components, a modular TORS simulator was constructed for short-duration hands-on simulations with the da Vinci SI robot. Sixteen surgeons of differing robotic skill levels, no experience (novice), prior experience, and formal robot training, participated in simulated tonsil and tongue base tumor resections. Video recordings of each participant were graded by a blinded robotically trained surgeon using a 35-point Global Evaluative Assessment of Robotic Surgery (GEARS) criterion adapted for the TORS simulator. RESULTS: Operators reporting formal robotic training or prior robot experience achieved significantly higher mean total GEARS scores compared to novice operators (32 vs. 20.5; P < .001). Overall, mean total GEARS scores correlated with reported experience level; novice operators scored 54% of total points at 19 (4.5), operators with prior experience scored 82.3% of total points at 28.8 (2.6), and robotically trained operators scored 97.1% of total points at 34 (1.7). CONCLUSION: With a GEARS criterion, our simulator successfully differentiated novice from experienced and robotically trained operators of the da Vinci SI robot during simulated tonsillectomy and base of tongue resections. These findings support the construct validity of this prototype simulator and offer a foundation for further testing of predictive validity. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:1588-1593, 2022.

Prognostic impact of socioeconomic status compared to overall stage for HPV-negative head and neck squamous cell carcinoma.

OBJECTIVE: To estimate the relative prognostic ability of socioeconomic status (SES) compared to overall stage for HPV-negative head and neck squamous cell carcinoma (HNSCC) MATERIALS AND METHODS: Data were obtained from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE). An empirical 4-category SES classification system was created. Cox proportional hazards models, survival gradients, Bayesian information criterion (BIC), and Harrell's C index were used to estimate the prognostic ability of SES compared to stage on overall survival (OS). RESULTS: The sample consisted of 1229 patients with HPV-negative HNSCC. Patients with low SES had significantly increased risk of mortality at 5 years compared to patients with high SES (HR 3.11, 95% CI 2.07-4.67; p < 0.001), and the magnitude of effect was similar to overall stage (HR 3.01, 95% CI 2.35-3.86; p < 0.001 for stage IV versus I). Compared to overall stage, the SES classification system had a larger total survival gradient (35.8% vs. 29.1%), similar model fit (BIC statistic of 7412 and 7388, respectively), and similar model discriminatory ability (Harrell's C index of 0.61 and 0.64, respectively). The association between low SES and OS persisted after adjusting for age, sex, race, alcohol, smoking, overall stage, tumor site, and treatment in a multivariable model (HR 2.96, 95% CI 1.92-4.56; p < 0.001). CONCLUSION: SES may have a similar prognostic ability to overall stage for patients with HPV-negative HNSCC. Future research is warranted to validate these findings and identify evidence-based interventions for addressing barriers to care for patients with HNSCC.

Clinical Outcomes of Patients With pT1-T2N0 Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: The objective of this study was to evaluate the clinical outcomes in a cohort of patients with early-stage oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: We conducted a retrospective analysis of patients with pT1-T2N0 (American Joint Committee on Cancer [AJCC] seventh edition) OTSCC treated from 2000 to 2018. Two-year actuarial rates of local regional control, cancer-specific survival, and overall survival were calculated for the entire cohort and patients with/without adjuvant radiation. RESULTS: Ninety-six patients met the criteria with a median follow-up of 4 years; 14 had adjuvant radiation, while 82 had surgery alone. Two-year local regional control was 82.7% (75.4% to 90.8%) for the entire cohort, 84.9% (77.8% to 93.2%) for surgery only, and 70.7% (50.2% to 99.6%) for patients with adjuvant radiation. Two-year progression-free survival was 82.7% (75.3% to 90.8%). Of the 20 patients with recurrence, 11 (55%) were successfully salvaged. CONCLUSION: Local regional recurrence remains modest in early-stage OTSCC, but salvage is possible with high survival rates. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Academic Affiliation and Surgical Volume Predict Survival in Head and Neck Cancer Patients Receiving Surgery.

OBJECTIVE: To determine whether the academic affiliation or surgical volume affects the overall survival (OS) of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) patients receiving surgery. METHODS: A retrospective study of 39 North Carolina Medical Centers was conducted. Treatment centers were classified as academic hospitals, community cancer centers, or community hospitals and were divided into thirds by volume. The primary outcome was 5-year OS. Hazard ratios (HR) were determined using Cox proportional hazard models, adjusting for demographics, tumor site, stage, insurance status, tobacco use, alcohol use, stage, chemotherapy, and radiation therapy. Patients were also stratified by stage (early stage and advanced stage). RESULTS: Patients treated at community cancer centers had significantly better 5-year OS (HR 0.68, 95% confidence interval [CI] = 0.48-0.98), and patients treated at academic hospitals trended toward better 5-year OS (HR 0.72, 95% CI = 0.50-1.04) compared to patients treated at community hospitals. The effect for academic affiliation on survival was more pronounced for patients with advanced stage cancer at diagnosis (HR 0.60, 95% CI = 0.37-0.95). There were no significant survival differences among early stage patients by treatment center type. Top-third (HR = 0.64, 95% CI = 0.42-0.96) centers by surgical volume had significantly better 5-year OS, and middle-third (HR = 0.71, 95% CI = 0.51-1.03) centers by volume trended toward better 5-year OS when compared to the bottom-third centers by volume. CONCLUSION: Patients treated at academic hospitals, community cancer centers, and hospitals in the top third by case volume have favorable survival for HPV-negative HNSCC. The effect for academic hospitals is most pronounced among advanced stage patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E479-E488, 2021.

Socioeconomic Status Drives Racial Disparities in HPV-negative Head and Neck Cancer Outcomes.

OBJECTIVES/HYPOTHESIS: To determine drivers of the racial disparity in stage at diagnosis and overall survival (OS) between black and white patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Retrospective cohort study. METHODS: Data were examined from of a population-based HNSCC study in North Carolina. Multivariable logistic regression and Cox proportional hazards models were used to assess racial disparities in stage at diagnosis and OS with sequential adjustment sets. RESULTS: A total of 340 black patients and 864 white patients diagnosed with HPV-negative HNSCC were included. In the unadjusted model, black patients had increased odds of advanced T stage at diagnosis (OR 2.0; 95% CI [1.5-2.5]) and worse OS (HR 1.3, 95% CI 1.1-1.6) compared to white patients. After adjusting for age, sex, tumor site, tobacco use, and alcohol use, the racial disparity persisted for advanced T-stage at diagnosis (OR 1.7; 95% CI [1.3-2.3]) and showed a non-significant trend for worse OS (HR 1.1, 95% CI 0.9-1.3). After adding SES to the adjustment set, the association between race and stage at diagnosis was lost (OR: 1.0; 95% CI [0.8-1.5]). Further, black patients had slightly favorable OS compared to white patients (HR 0.8, 95% CI [0.6-1.0]; P = .024). CONCLUSIONS: SES has an important contribution to the racial disparity in stage at diagnosis and OS for HPV-negative HNSCC. Low SES can serve as a target for interventions aimed at mitigating the racial disparities in head and neck cancer. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1301-1309, 2021.

Age and risk of recurrence in oral tongue squamous cell carcinoma: Systematic review.

The incidence of oral tongue squamous cell carcinoma has been increasing in young patients (≤45 years) without a clear etiologic driver. It is unknown if younger patients have an increased risk of recurrence compared to older patients. A literature search was conducted through January 2020 using PubMed/MEDLINE, Embase, Cochrane, Scopus, Science Direct, and clinicaltrials.gov. This review was registered with PROSPERO (ID: CRD42020167498) and the PRISMA statement was followed. Studies were eligible for inclusion if they assessed risk of recurrence by age using a time-to-event analysis, used an age cutoff of ≤45 years or less for the younger cohort, and limited the analysis to the oral tongue subsite. Data were extracted independently by two reviewers using a form with a prespecified list of variables. There were 13 articles that met criteria for the qualitative synthesis (n = 1763 patients). The reported 5-year rates of disease-free survival ranged from 30% to 72% for the younger cohorts and 42% to 81% for the older cohorts. Three studies reported a statistically significant increased risk of recurrence in younger patients, three studies reported a nonsignificant increased risk in younger patients, and seven studies reported a similar risk in younger patients based on the time-to-event analyses. There may be an increased risk of recurrence for younger patients with oral tongue cancer. A definitive conclusion is precluded by limitations among individual studies, and additional research is warranted to examine this question.

Access to preventive care services and stage at diagnosis in head and neck cancer.

BACKGROUND: Decreased access to preventive care services has been proposed as a mechanism for the association between low socioeconomic status (SES) and advanced stage at diagnosis in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective analysis of patients diagnosed with HNSCC in North Carolina between 2002 and 2006. RESULTS: A total of 1108 patients with HNSCC were included in the study. In the multivariable analysis, use of annual routine dental services (OR 0.7, 95% CI 0.5-0.9) and colonoscopy in the past 10 years (OR 0.7, 95% CI 0.5-0.9) were associated with lower odds of advanced T stage at diagnosis. Having no insurance (OR 1.8, 95% CI 1.1-2.9), an income <$20 000 (OR 1.6 95% CI 1.03-2.6), and >10 pack-years tobacco use (OR 1.5, 95% CI 1.04-2.2) were associated with advanced T stage at diagnosis. CONCLUSION: Use of preventive care services and SES independently predict stage at diagnosis in HNSCC.

Prescription and Usage Pattern of Opioids after Thyroid and Parathyroid Surgery.

OBJECTIVE: We seek to characterize the prescribing patterns of opioids, opioid consumption, and pain severity after thyroid and parathyroid surgery. We also aim to determine if a relationship exists between preoperative medication use and postoperative pain or opioid consumption. STUDY DESIGN: Case series with chart review. SETTING: Academic university hospital. SUBJECTS AND METHODS: Medical records of 237 adult patients undergoing thyroid and parathyroid surgery were included. Clinicopathologic data were collected, including pain scores, preoperative medications, and inpatient pain medications. RESULTS: The mean maximum pain score was 5.74 and varied by surgery type (range, 0-10). Mean pain score decreased to 2.61 upon discharge (0-8) and to 0.51 at the first postoperative visit. Patients with a length of stay exceeding 1 day had significantly higher maximum pain scores than those with a length of stay of 0 or 1 day (8 vs 5.58, P < .001). Morphine milligram equivalents while in the hospital averaged 25.4 per day and were significantly influenced by preoperative opioid use (0-202). Acetaminophen/oxycodone was the most commonly prescribed opioid. The mean number of pills prescribed postoperatively was 43.1 (0-120). CONCLUSION: In our population, patients are discharged with opioid prescriptions that may be in excess of their requirements following thyroid and parathyroid surgery. Preoperative opioid use was associated with higher postoperative pain score and, on multivariate analysis, greater inpatient opioid consumption. Further investigation is warranted to ensure that we are prescribing opioids appropriately following thyroid and parathyroid surgery.

Post-diagnosis aspirin use and survival in veterans with head and neck cancer.

BACKGROUND: Our objective was to determine the effect of post-diagnosis aspirin use on survival in veterans with head and neck squamous cell carcinoma. METHODS: Retrospective cohort study of 584 veterans with head and neck squamous cell carcinoma treated at the Washington DC VA Medical Center between 1995 and 2015. Charts were queried for clinical-pathologic data, aspirin prescriptions, and outcome. The Kaplan-Meier method was used to determine overall survival (OS) and disease-specific survival (DSS) among aspirin users and nonusers. RESULTS: A total of 329 patients met inclusion criteria. Primary subsites included oropharynx (n = 143), larynx (n = 105), oral cavity (n = 62), and hypopharynx (n = 19). Eighty-four patients were aspirin users (25.5%). Aspirin users demonstrated significantly better 3-year OS and DSS (78.6% and 88.1%) compared to nonaspirin users (OS: 55.9% and DSS: 70.2%; P = .0003 and P = .0019, respectively). On multivariate analysis, aspirin use remained independently associated with improved survival. CONCLUSION: Aspirin use following diagnosis and curative treatment of head and neck squamous cell carcinoma is associated with improved OS and DSS.

The Use of Tomosynthesis in the Global Study of Knee Subchondral Insufficiency Fractures.

RATIONALE AND OBJECTIVES: Subchondral insufficiency fractures (SIF), previously termed spontaneous osteonecrosis of the knee, are marked by a sudden onset of severe pain. Other than the size of the lesion, prediction for progression to joint replacement is difficult. The objective was to determine if quantitative analysis of bone texture using digital tomosynthesis imaging would be useful in predicting more rapid progression to joint replacement. MATERIALS AND METHODS: Tomosynthesis studies of 30 knees with documented SIF were quantified by fractal, mean intercept length (MIL), and line fraction deviation analyses. Fractal dimension, lacunarity, MIL, and line fraction deviation variables measured from these analyses were then correlated to short interval progression to joint replacement surgery. RESULTS: Higher odds for joint replacement were related to higher values of the standard deviation of slope lacunarity and to morphometric measures (eg, MIL). CONCLUSIONS: Using digital tomosynthesis images for bone texture assessment may help distinguish condylar bone response in SIF, potentially acting as a clinically relevant predictive tool. In the future, contrasting SIF to the more gradual long-term process of osteoarthritis, there may be a better understanding of the different mechanisms for the two conditions.

Normative data of incus and stapes displacement during middle ear surgery using laser Doppler vibrometry.

OBJECTIVES: To report normative data for incus and stapes motion using laser Doppler vibrometry (LDV) during middle ear surgery and to discuss possible limitations of the procedure. STUDY DESIGN: Institutional review board-approved, retrospective study of data from patients undergoing the Envoy Esteem implantable device at 3 institutions. SETTING: Quaternary referral health system. ELIGIBILITY CRITERIA: patients sucsessfully implanted with an Esteem device. METHODS: Data from 70 patients undergoing the Envoy Esteem procedure were reviewed. Sound at 100 dB and 50 frequencies ranging from 125 to 8,000 Hz were used during the procedure. LDV was performed to measure the displacment of the body of the incus and the posterior crus of the stapes to assess whether there was sufficient ossicular mobility to allow for implantation. RESULTS: The average displacement of the ossicles for all 70 patients was collected and analyzed. The trend was an average displacement around 100 nm from 125 to 500 Hz for both the incus and stapes with a linear decline starting at 1,000 Hz for the incus and 500 Hz for the stapes, with slightly greater displacement of the stapes at higher frequencies. CONCLUSION: This is the first article to report in vivo measures of ossicular mobility. These data help to understand the micromechanics of ossicular motion as well as the use and limitations of LDV. This information may lead to a prescreening process for implanted middle ear devices that function by overdriving the stapes.