Breaking Ground in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Novel Therapies Beyond PD-L1 Immunotherapy.

The treatment for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (anti-PD1) with or without chemotherapy has led to an improvement in survival. Yet, despite this therapeutic advancement, only 15%-19% of patients remain alive at four years, highlighting the poor survival and unmet need for improved therapies for this patient population. Some of the key evolving novel therapeutics beyond anti-PD1 in R/M HNSCC have included therapeutic vaccine therapies, bispecific antibodies/fusion proteins and multitargeted kinase inhibitors, and antibody-drug conjugates (ADCs). Multiple concurrent investigations of novel therapeutics for patients with R/M HNSCC beyond anti-PD(L)1 inhibition are currently underway with some promising early results. Beyond immune checkpoint inhibition, novel immunotherapeutic strategies including therapeutic vaccines ranging from targeting human papillomavirus-specific epitopes to personalized neoantigen vaccines are ongoing with some early efficacy signals and large, randomized trials. Other novel weapons including bispecific antibodies, fusion proteins, and multitargeted kinase inhibitors leverage multiple concurrent targets and modulation of the tumor microenvironment to harness antitumor immunity and inhibition of protumorigenic signaling pathways with emerging promising results. Finally, as with other solid tumors, ADCs remain a promising therapeutic intervention either alone or in combination with immunotherapy for patients with R/M HNSCC. With early enthusiasm across novel therapies in R/M HNSCC, results of larger randomized trials in R/M HNSCC are eagerly awaited.

A Mixed-Method Approach to Explore Successful Recruitment and Treatment of Minority Patients on Therapeutic Cancer Clinical Trials at a Tertiary Referral Center Using Photo-Elicitation Interviews.

Introduction: Under-represented minority patients (URM) enroll in cancer clinical trials (CCT) at low rates. To gain insight into barriers and facilitators to CCT enrollment, we conducted a mixed method study of URM patients who were successfully treated on a therapeutic CCT from 2018-2021 at all institutional sites. Methods: A retrospective chart review of 270 minority patients was conducted to identify patient demographics and characteristics. All living URM patients were requested to participate in a survey and qualitative interview using a photo elicitation technique. Results: Most patients who participated in a CCT were patients with solid tumors, metastatic disease, and did not live in a rural area. Survey data showed that the two most significant drivers of CCT enrollment were potential of benefit to self and to others (altruism). Direct recommendation from a healthcare provider to participate in CCT was critical. URM patients enrolled on a CCT experience a significant burden of symptoms and financial distress. Key themes identified from the interviews that motivated patients to participate included chance for cure, staying positive, altruism and advancement of science, and having diverse representation in research. Patient-level facilitators to participation included social support, cost coverage, and limited treatment options. Sytematic facilitators identified included minimizing logistical barriers, decentralizing cancer clinical trials, increasing awareness via patient narratives, diversifying research staff, minimizing cost, and being clear on puropose and benefit of the trial. Conclusion: Success stories of minority recruitment can provide useful information to enhance minority accrual. Photo elicitation interviews provide rich narratives of patient experience.

Treatment outcomes of single-fraction stereotactic radiosurgery for adenoid cystic carcinoma: a case series of 55 patients.

PURPOSE: This study aimed to analyze the treatment outcomes of single-fraction stereotactic radiosurgery (SRS) for adenoid cystic carcinoma patients. METHODS: Retrospective analysis was conducted for 55 patients with 66 lesions. SRS intentions were categorized as definitive, adjuvant, salvage, and palliative. Tumor control was defined as local (within 50% isodose line), marginal (outside 50% isodose line), and distant (metastasis outside head/neck). RESULTS: The median age was 60 years (range 21-85), with 53% males. Tumor origin was head/neck for 88% and trachea/lung for 12%. 61% were recurrent lesions. Median interval from diagnosis to SRS was 14 months. Preceding surgery was performed in 30%. SRS was administered as definitive (30 lesions), adjuvant (13), salvage (19), and palliative (4). SRS was used as a boost to external beam radiation therapy (EBRT) in 39%. Concurrent chemotherapy was administered in 26%. 5-, 10-, and 15-year local control rates were 60%, 33%, and 27%, respectively; local/marginal control rates were 29%, 13%, and 10%. For recurrent lesions treated with SRS without EBRT, 5-year local control rate was 14%, and local/marginal control rate was 5%. For recurrent lesions treated with SRS and EBRT, 5-year local control rate was 100%, and local/marginal control rate was 40%. The rate of distant failure after SRS was 40%. Older age and distant metastasis before SRS were negative factors for overall survival. CONCLUSION: SRS provided a high rate of local tumor control, but marginal failure was frequent. Integrating SRS with added EBRT exhibits potential for enhancing local and local/marginal tumor control, particularly in recurrent cases.

Patterns and distribution of regional nodal involvement and recurrence in a surgically treated oropharyngeal squamous cell carcinoma cohort at a tertiary center.

OBJECTIVES: To investigate and describe the patterns of regional metastases and recurrences after surgical treatment of oropharyngeal squamous cell cancer (OPSCC). MATERIALS AND METHODS: Retrospective study of patients diagnosed with OPSCC from 2006 to 2021 at a tertiary referral center. Only patients treated with surgery including a neck dissection were included. Patients with unknown human papillomavirus (HPV) status, prior head and neck cancer, distant metastases, or synchronous head and neck cancer were excluded. RESULTS: A total of 928 patients were included. 89% were males, the average age was 58.6 years (range: 25.2-87.5), 874 (94%) were HPV(+), and 513 (55.3%) had a tonsil cancer. Among cN + patients, the most commonly involved levels at presentation were level II (85.2%), level III (33.3%), and level IV (9.4%). In cN0 patients, metastases were only observed in level II (16.2%) and level III (9.2%). Nodal recurrence occurred in 48 (5.2%) patients after a median time of 1.0 years (interquartile range: 0.6-2.0). Nodal recurrence incidence was similar in HPV(+) and HPV(-) patients (5.0% vs. 7.4%, p = 0.44). The most common levels for regional recurrence were ipsilateral level II (45.8%), contralateral level II (43.8%), and ipsilateral level V (25.0%). Multivariable analysis revealed that pN was a significant predictor for regional recurrence (p = 0.02). CONCLUSION: There is no difference in the distribution of regional metastases and recurrences in HPV(+) and HPV(-) OPSCC patients. Our findings align with the established understanding that regional metastases predominantly manifest in the ipsilateral level II-IV at presentation. Moreover, the data support the clinical recommendation to restrict elective neck dissection in cN0 patients to ipsilateral levels IIa and III, excluding level IIb. Regional recurrence is significantly associated with pN status.

Real-World Implementation of Best-Evidence Cancer Distress Management: Truly Comprehensive Cancer Care.

BACKGROUND: Cancer distress management is an evidence-based component of comprehensive cancer care. Group-delivered cognitive behavioral therapy for cancer distress (CBT-C) is the first distress treatment associated with replicated survival advantages in randomized clinical trials. Despite research supporting patient satisfaction, improved outcomes, and reduced costs, CBT-C has not been tested sufficiently within billable clinical settings, profoundly reducing patient access to best-evidence care. This study aimed to adapt and implement manualized CBT-C as a billable clinical service. PATIENTS AND METHODS: A stakeholder-engaged, mixed-methods, hybrid implementation study design was used, and the study was conducted in 3 phases: (1) stakeholder engagement and adaptation of CBT-C delivery, (2) patient and therapist user testing and adaptation of CBT-C content, and (3) implementation of practice-adapted CBT-C as a billable clinical service focused on evaluation of reach, acceptability, and feasibility across stakeholder perspectives. RESULTS: A total of 40 individuals and 7 interdisciplinary group stakeholders collectively identified 7 primary barriers (eg, number of sessions, workflow concerns, patient geographic distance from center) and 9 facilitators (eg, favorable financial model, emergence of oncology champions). CBT-C adaptations made before implementation included expanding eligibility criteria beyond breast cancer, reducing number of sessions to 5 (10 total hours), eliminating and adding content, and revising language and images. During implementation, 252 patients were eligible; 100 (40%) enrolled in CBT-C (99% covered by insurance). The primary reason for declining enrollment was geographic distance. Of enrollees, 60 (60%) consented to research participation (75% women; 92% white). All research participants completed at least 60% of content (6 of 10 hours), with 98% reporting they would recommend CBT-C to family and friends. CONCLUSIONS: CBT-C implementation as a billable clinical service was acceptable and feasible across cancer care stakeholder measures. Future research is needed to replicate acceptability and feasibility results in more diverse patient groups, test effectiveness in clinical settings, and reduce barriers to access via remote delivery platforms.

Clinicopathologic Factors and Their Association with Outcomes of Salivary Duct Carcinoma: A Multicenter Experience.

Purpose: This series reports long-term clinical outcomes of patients with salivary duct carcinoma (SDC), which is associated with a poor prognosis. Methods and Materials: Eighty-nine patients with SDC were treated with curative intent from February 5, 1971, through September 15, 2018. Kaplan-Meier and competing risk analyses were used to estimate locoregional control, distant metastasis-free survival (DMFS), progression-free survival, and overall survival (OS). Cox regression analyses of disease and treatment characteristics were performed to discover predictors of locoregional control, DMFS, and OS. Results: Median follow-up was 44.1 months (range, 0.23-356.67). The median age at diagnosis was 66 years (interquartile range, 57-75). Curative surgery followed by adjuvant radiation therapy was performed in 73 patients (82%). Chemotherapy was delivered in 26 patients (29.2%). The 5-year local recurrence and distant metastasis rates were 27% and 44%, respectively, with death as a competing risk. Distant metastasis was associated with lymph node-positive disease (hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.38-7.23; P = .006), stage IV disease (HR, 4.78; 95% CI, 1.14-20.11; P = .033), perineural invasion (HR, 4.56; 95% CI, 1.74-11.97; P = .002), and positive margins (HR, 9.06; 95% CI, 3.88-21.14; P < .001). Median OS was 4.84 years (95% CI, 3.54-7.02). The 5-year OS was 42%. Reduced OS was associated with lymphovascular space invasion (HR, 3.49; 95% CI, 1.2-10.1; P = .022), perineural invasion (HR, 2.05; 95% CI, 1.06-3.97; P = .033), positive margins (HR, 2.7; 95% CI, 1.3-5.6; P = .011), N2 disease (HR, 1.88; 95% CI, 1.03-3.43; P = .04), and N3 disease (HR, 11.76; 95% CI, 3.19-43.3; P < .001). Conclusions: In this single-institution, multicenter retrospective study, the 5-year survival was 42% in patients with SDC. Lymphovascular space invasion, lymph node involvement, and higher staging at diagnosis were associated with lower DMFS and OS.

Adenoid cystic carcinoma of the head and neck: Patterns of recurrence and implications for intensity-modulated radiotherapy.

BACKGROUND: We seek to inform radiotherapy (RT) delivery for adenoid cystic carcinoma of the head and neck (ACC) by evaluating RT techniques and recurrence patterns. METHODS: We identified patients with ACC treated with curative-intent RT from 2005 to 2021. Imaging was reviewed to determine local recurrence (LR). RESULTS: Ninety-one patients were included. The 5-year LR risk was 12.2% (6.6-22.7). One patient each experienced a marginal and out-of-field recurrence. Patients receiving >60 Gy postoperatively had a 5-year LR risk of 0% compared to 10.7% (4.2-27.2) with ≤60 Gy. Those receiving 70 and <70 Gy definitively had a 5-year LR risk of 15.2% (2.5-91.6) and 33.3% (6.7-100.0), respectively. No patients had regional nodal failure. CONCLUSIONS: Modern, conformal RT for ACC results in low rates of LR. Doses >60 and 70 Gy may improve control in the postoperative and definitive settings, respectively. Elective nodal treatment can be omitted in well-selected patients.

Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Failure to recognize symptoms of non-human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(-)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(-)OPSCC. METHODS: Retrospective review at a tertiary care center. Patients with HPV(-)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care. RESULTS: Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32-127 days), with a median latency of 30 days (IQR = 12-61 days) from symptom onset to first presentation and 19.5 days (IQR = 4-46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis. CONCLUSIONS: Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(-)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(-)OPSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1394-1401, 2023.

Capecitabine for Salvage Treatment of Patients With Heavily Pretreated Human Papillomavirus-Associated Oropharynx Cancer With Distant Metastases.

Background: Patients with metastatic human papillomavirus-associated oropharyngeal cancer (HPV-OPC) have a median overall survival exceeding 2 years and are often candidates for multiple lines of palliative therapy. With the approval of immunotherapy as first-line treatment, salvage therapeutic options are limited. We describe our experience using capecitabine as salvage therapy for patients with recurrent or metastatic (R/M) HPV-OPC. Methods: We performed a retrospective study of patients with R/M HPV-OPC with distant metastatic disease. Eligible patients were identified from a medical oncology clinical database. Demographic and clinical data were abstracted from the medical record. Survival probabilities were estimated with the Kaplan-Meier method. Results: 10 patients were identified. Sites of metastatic disease included lung, liver, mediastinal lymph nodes, bone, abdominal lymph nodes, and soft tissue. Most patients received capecitabine as fourth-line treatment. The median duration from start of capecitabine therapy until death was 10.5 months. Best treatment response was as follows: partial responses (PR) were seen in 4 of 10 (40%), stable disease (SD) in 3 of 10 (30%), and progressive disease (PD) in 2 of 10 (20%). The clinical benefit rate (CR + PR + SD) was 70%. Reasons for discontinuation included disease progression (n = 8) and side effects (n = 2). One patient notably had prolonged benefit from capecitabine and continued to be on treatment for 34 months total. Conclusions: Capecitabine is a potential salvage treatment for heavily pretreated patients with R/M HPV-OPC, with some patients experiencing prolonged response. Clinical or molecular predictors of response would be helpful to identify patients likely to benefit; a larger prospective study would be useful to confirm efficacy in this patient population.

Low postoperative lymphocyte count increases risk of progression in human papillomavirus associated oropharyngeal cancer.

BACKGROUND: We aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC). METHODS: Retrospective cohort at a tertiary center, 2006-2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC. RESULTS: All 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109  cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post-RT (N = 141): 0.68 (0.35) and long-term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03-14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04-6.67, p = 0.04). CONCLUSIONS: Lower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.

A prospective, randomized trial of patient-reported outcome measures to drive management decisions in hematology and oncology.

Background: Clinicians have limited time during patient encounters which can result in patients' concerns not being addressed. This study's objective was to test whether an electronic patient-reported outcome quality of life tool (PROQOL) in which patients identify their primary concern during clinic visits improves cancer patient quality of life (QOL). Patients and methods: This single center non-blinded prospective clinical trial randomized patients (2:1) to PROQOL versus usual care (UC). Two patient cohorts were enrolled: those with hematologic malignancies (multiple myeloma [MM] or light chain amyloidosis [AL]) and solid tumors (head and neck [H/N] or gynecologic [GYN] malignancies). Primary endpoint was patient-reported QOL at 12 months measured by a single-item Linear Analog Self-Assessment. Value to patients and impact on clinician workflow was measured using a "was it worth it" survey. The study was powered to detect a 0.5 standard deviation difference between groups. Results: Overall 383 patients were enrolled, 171 with MM, 62 AL, 113 GYN, and 37 H/N between July 2016 and April 2018, with 12-month follow-up. There were 171 (44.6%) male patients and median age was 62 years (range 31-87). The most often selected concern was physical health (30.9%), and second was cancer diagnosis and treatment (29.1%). Mean QOL was 7.12 for PROQOL and 6.98 for UC (0-10 scale) at 12 months, with no between-group difference overall (p = 0.56) or within hematologic or solid tumor cohorts, respectively. Among patients, 74% thought the PROQOL tool was worthwhile, 86% would choose PROQOL again, and 81% would recommend it to others. Among clinicians, 95% responded that PROQOL was worthwhile and did not think that PROQOL negatively impacted their workflow. Conclusions: Although we did not demonstrate a QOL difference between PROQOL and UC groups; the PROQOL tool held considerable value in identifying patients' main concerns over time and was worthwhile for patients and clinicians.

Evaluation of pembrolizumab monotherapy in patients with previously treated advanced salivary gland carcinoma in the phase 2 KEYNOTE-158 study.

AIM: We evaluated pembrolizumab monotherapy in patients with advanced salivary gland carcinoma on the phase 2 KEYNOTE-158 study (NCT02628067). METHODS: Eligible patients had histologically/cytologically confirmed advanced salivary gland carcinoma with prior failure or intolerance to standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1., and ECOG performance status 0-1. Patients were enrolled irrespective of tumour PD-L1 expression. Patients received pembrolizumab 200 mg Q3W for up to 35 cycles (∼2 years). Radiographic imaging occurred every 9 weeks through month 12, then every 12 weeks. PD-L1 positivity was defined as combined positive score ≥1 (evaluated using PD-L1 IHC 22C3 pharmDx). The primary endpoint was objective response rate per RECIST v1.1. RESULTS: In total, 109 patients were enrolled (PD-L1-positive, 25.7%). At the data cutoff (October 5, 2020), median follow-up was 53.3 (range, 50.8-56.3) months. Objective response rate was 4.6% (95% CI, 1.5-10.4%) among all patients (complete response, n = 1; partial response, n = 4) and was 10.7% (95% CI, 2.3-28.2%) in patients with PD-L1-positive disease and 2.6% (95% CI, 0.3-9.1%) in patients with PD-L1-negative disease. Duration of response was ≥24 months for all 5 responders; median duration of response was not reached (range, 25.1-49.8+ months). Median progression-free survival and overall survival were 4.0 (95% CI, 2.6-4.2) and 21.1 (95% CI, 15.9-25.5) months, respectively. Treatment-related adverse events occurred in 75.2% (grade 3-4, 15.6%; grade 5, 0%) of patients. Immune-mediated adverse events occurred in 22.0% of patients (grade 3, 5.5%; grade 4-5, 0). CONCLUSIONS: A small subset of patients with advanced salivary gland carcinoma treated with pembrolizumab had a response; all had response duration ≥2 years. The safety profile of pembrolizumab was manageable.

Emerging Disparities in Prevention and Survival Outcomes for Patients with Head and Neck Cancer and Recommendations for Health Equity.

PURPOSE OF REVIEW: The aim of this review is to describe less known and emerging disparities found in the prevention and survival outcomes for patients with head and neck cancer (HNC) that are likely to play an increasingly important role in HNC outcomes and health inequities. RECENT FINDINGS: The following factors contribute to HNC incidence and outcomes: (1) the effect of rurality on prevention and treatment of HNC, (2) dietary behavior and nutritional factors influencing the development of and survival from HNC, and (3) barriers and benefits of telehealth for patients with HNC. Rurality, nutrition and diet, and telehealth usage and access are significant contributors to the existing health disparities associated with HNC. Population and culturally specific interventions are urgently needed as well as more research to further define the issues and develop appropriate population and individual level solutions.

Detectable Postoperative Circulating Tumor Human Papillomavirus DNA and Association with Recurrence in Patients With HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: The purpose of our study is to determine the rate of detectability of ctHPVDNA after surgery but before adjuvant therapy in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC) and to investigate whether detectable ctHPVDNA at this time point may be associated with risk of recurrence. METHODS AND MATERIALS: We examined prospectively collected samples from patients with OPSCC in a blinded fashion using a multianalyte polymerase chain reaction assay. We collected 45 samples from patients with HPV(+)OPSCC preop (before any treatment) and 159 samples postop (before or at the start of adjuvant radiation therapy). We identified samples via the radiation oncology biobank or via participation in a clinical trial. Radiation therapy consisted of 60 Gy ± cisplatin or de-escalation (30 Gy to 36 Gy in 20 bid fractions + docetaxel). For our preliminary analysis, 32 patients had paired samples available pre- and postop. We performed additional exploratory analyses including associations of patient and tumor characteristics with recurrence using Cox proportional hazards models for all 159 postop samples. We compared detectability of ctHPVDNA across groups using logistic regression. We used Kaplan-Meier to estimate recurrence-free survival. RESULTS: In a paired analysis of 32 pre- and postop timepoints, 94% of patients had detectable ctHPVDNA preop and 41% did postop. Recurrence-free survival at 18 months was 83% (95% confidence interval, 47%-95%) for patients with detectable postop ctHPVDNA compared with 100% for patients with undetectable postop ctHPVDNA (P = .094). In an exploratory analysis of nonpaired postop samples, ctHPVDNA was detectable in 26% of patients (41 of 159) (median of 22 days postop). Age (odds ratio,1.06, P = .025), lymphovascular space invasion (odds ratio, 3.17, P = .011) and extranodal extension (odds ratio = 5.67, P = .001) were associated with detectable ctHPVDNA after surgery. Detectable postop ctHPVDNA was significantly associated with recurrence-free survival (P < .001). CONCLUSION: Among patients with detectable preop ctHPVDNA, a significant proportion have detectable postop ctHPVDNA in paired postop samples collected before the initiation of adjuvant radiation therapy. Future prospective study is warranted to investigate the association of detectable postop ctHPVDNA with recurrence, including in comparison to established clinical and pathologic risk factors.

The role of total parotidectomy in high-grade parotid malignancy: A multisurgeon retrospective review.

PURPOSE: Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection. MATERIALS & METHODS: Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported. RESULTS: 75 patients with median follow-up time of 47 months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed recurrence rate was 5.3% (4/75). Regional lymph node recurrence rate was also 5.3% (4/75). Rate of distant metastasis was 30.6% (23/75). The overall disease free survival rate for all patients at 2 and 5 years were 71% and 60% respectively. CONCLUSION: Parotid lymph node metastasis occurred at a similar rate to cervical lymph node metastasis (46.7% and 49.3%, respectively). Deep lobe parotid nodal metastasis occurred in nearly a quarter of patients and can occur without superficial parotid nodal metastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.

Assessment of Discrimination, Bias, and Inclusion in a United States Hematology and Oncology Fellowship Program.

Importance: Medical trainees frequently experience discrimination. Understanding their experiences is essential to improving learning environments. Objective: To characterize trainee experiences of discrimination and inclusion to inform graduate medical education (GME) policies. Design, Setting, and Participants: This qualitative study used an anonymous telephone interview technique to gather data from hematology and oncology fellows. All current trainees and recent graduates were eligible. Interviews were conducted anonymously with interviewer and participant in separate locations and recorded and transcribed. Data were analyzed in an iterative process into major themes using a general inductive analysis approach. Demographic information was obtained via anonymous survey. Data collection and analysis were conducted from July 2018 to November 2019. Main Outcomes and Measures: Emergent themes illustrating bias and inclusion in a GME program. Results: Among 34 fellows and recent graduates who were approached for this study, 20 consented and 17 were interviewed. Of those interviewed, 10 were men, and the median (range) age was 32 (29-53) years. The racial and ethnic distribution included 6 Asian individuals, 2 Black individuals, 3 Hispanic individuals, 2 multiracial individuals, and 4 White individuals. All fellows reported having experienced and/or witnessed discriminatory behavior. The themes elucidated were (1) foreign fellows perceived as outsiders, (2) US citizens feeling alien at home, (3) gender role-typing, (4) perception of futility of reporting, (5) diversity and inclusion, and (6) coping strategies. The majority of reported biases were from patients. Only 1 trainee reported any incidents. Reasons for not reporting were difficulty characterizing discrimination and doubt action would occur. Participants reported that diversity of cotrainees, involvement in committees, and open discussions promoted inclusivity. Conclusions and Relevance: In this study, reports of discriminatory behavior toward trainees were common. The anonymous hotline methodology cultivated a safe environment for candid discussions. These findings suggest that GME programs should assess their learning climate regarding bias and inclusivity anonymously and develop processes to support trainees.

Disease Profile and Oncologic Outcomes After Delayed Diagnosis of Human Papillomavirus-Associated Oropharyngeal Cancer.

OBJECTIVE: Diagnostic delay in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset. STUDY DESIGN: This is a retrospective cohort study of HPV(+)OPSCC patients receiving intent-to-cure treatment (including surgery ± adjuvant therapy or primary chemoradiation). SETTING: 2006-2016, tertiary care center. METHODS: Tumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan-Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes. RESULTS: In total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on Cancer (AJCC) clinical stage at presentation (P < .01 for both). At 5 years, rates of overall survival, cancer-specific survival, progression-free survival, and distant metastases-free survival in the delayed diagnosis cohort were 80%, 90%, 80%, and 89%, respectively. A >12-month delay in diagnosis did not significantly impact overall survival (adjusted hazard ratio [aHR], 1.16; 95% CI, 0.58-2.31), cancer-specific survival (aHR, 0.83; 95% CI, 0.29-2.39), progression-free survival (aHR, 1.15; 95% CI, 0.56-2.37), or distant metastases-free survival (aHR, 1.00; 95% CI, 0.42-2.40) after adjusting for age, sex, and clinical AJCC stage (P > .05 for all). CONCLUSIONS: Delayed diagnosis of HPV(+)OPSCC is associated with greater burden of disease at presentation, but oncologic outcomes remain favorable across treatment modalities. When appropriate, intent-to-cure therapy should be pursued despite diagnostic delay. LEVEL OF EVIDENCE: Level III.

Survival outcomes in locally advanced cutaneous squamous cell carcinoma presenting with clinical perineural invasion alone.

BACKGROUND: Cutaneous squamous cell carcinomas (CSCC) involving the head and neck are common, but initial presentation or recurrence limited to the cranial nerves is rare. METHODS: We conducted a retrospective study of 21 patients with clinical perineural invasion (PNI) from CSCC and no measurable disease by RECIST 1.1. Patients treated with radiotherapy or chemoradiotherapy were included. RESULTS: The median time from symptom onset until diagnosis was 13.0 months (2.6-83.1). All patients received radiotherapy. Fourteen received concurrent systemic therapy. The median follow-up time was 30.5 months (1.1-106.0). Ten patients recurred, with the majority being locoregional. The 2-year overall survival rate was 85%. The median progression-free survival (PFS) was 21.5 months with an estimated 2-year PFS of 44.5% (95%CI: 22.3-66.8). CONCLUSIONS: CSCCs with clinical PNI alone are difficult to diagnose and can have a long interval between appearance of symptoms and diagnosis. They can successfully be treated with chemoradiotherapy. However, many patients still suffer from locoregional recurrences.