Association Between Social Determinants of Health, Distance from Treatment Center, and Treatment Type with Outcomes in Human Papillomavirus Associated Oropharyngeal cancer.

OBJECTIVES: Social determinants of health (SDOH) can influence access to cancer care, clinical trials, and oncologic outcomes. We investigated the association between SDOH, distance from treatment center, and treatment type with outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] patients treated at a tertiary care center. STUDY DESIGN: Retrospective review. METHODS: HPV(+)OPSCC patients treated surgically from 2006 to 2021 were selected from our departmental Oropharyngeal Cancer RedCap database. Demographic data, treatment, and oncologic outcomes were extracted. Distance was calculated in miles between the centroid of each patient zip code and our hospital zip code (zipdistance). RESULTS: 874 patients (89 % male; mean age: 58 years) were identified. Most patients (96 %) reported Non-Hispanic White as their primary race. 204 patients (23 %) had a high-school degree or less, 217 patients (25 %) reported some college education or a 2-year degree, 153 patients (18 %) completed a four-year college degree, and 155 patients (18 %) had post-graduate degrees. Relative to those with a high-school degree, patients with higher levels of education were more likely to live further away from our institution (p < 0.0001). Patients who received adjuvant radiation therapy elsewhere lived, on average, 104 miles further away than patients receiving radiation at our institution (Estimate 104.3, 95 % CI 14.2-194.4, p-value = 0.02). In univariable Cox PH models, oncologic outcomes did not significantly differ by zipdistance. CONCLUSIONS: Education level-and access to resources-varied proportionally to a patient's distance from our center. Patients travelling further distances for surgical management of OPSCC were more likely to pursue adjuvant radiation therapy at an outside institution. Distance traveled was not associated with oncologic outcomes. Breaking down barriers to currently excluded populations may improve access to clinical trials and improve oncologic outcomes for diverse patient populations.

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.

Genomic Immune Evasion: Diagnostic and Therapeutic Opportunities in Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell cancers (HNSCCs) represent a diverse group of tumors emerging within different mucosal surfaces of the oral cavity, nasopharynx, oropharynx, larynx, and hypopharynx. HNSCCs share common clinical risk factors and genomic features, including smoking, alcohol, age, male sex, aneuploidy, and TP53 mutations. Viral initiating and contributing events are increasingly recognized in HNSCCs. While both Epstein-Barr Virus (EBV) and human papilloma virus (HPV) are observed, EBV is more frequently associated with nasopharyngeal cancers whereas HPV is associated with oropharyngeal cancers. HNSCCs are associated with high tumor mutational burden and loss of tumor suppressor gene function, especially in TP53 and X-linked genes. Multiple lines of evidence suggest that HNSCCs are subject to immunologic surveillance and immune-induced evolutionary pressure that correlate with negative clinical outcomes. This review will discuss genomic mechanisms related to immune-mediated pressures and propose prognostic and therapeutic implications of detectable immune escape mechanisms that drive tumorigenesis and disease progression.

Lenvatinib as a Therapeutic Option in Unresectable Metastatic Pheochromocytoma and Paragangliomas.

Context: Metastatic pheochromocytomas and paragangliomas (mPPGL) are rare vascular neuroendocrine tumors that highly express vascular growth factors. Systemic treatment options in cases of unresectable multisite disease are limited. Multikinase inhibitors that inhibit angiogenesis, such as lenvatinib, have proven effective in several other malignancies, and may be a viable option for mPPGL. Objective: We aimed to evaluate the efficacy of lenvatinib as salvage therapy in mPPGLs. Methods: This was a retrospective analysis of mPPGL patients ≥ 18 years of age who received lenvatinib from 2015 to 2020 at a tertiary referral center. Patients were started on lenvatinib 20 mg daily and dose was adjusted according to tolerance or disease progression. Results: Eleven patients were included. Median treatment duration was 14.7 months (95% CI, 2.3-NE). Treatment was discontinued due to disease progression, adverse events, or death. Overall survival at 12 months was 80.8% (95% CI, 42.3-94.9%) but its median was not reached. Median progression-free survival was 14.7 months (95% CI, 1.7-NE). Among the 8 patients with measurable disease, overall response rate was 63%, as 5/8 experienced a partial response and 3/8 had stable disease. Worsening hypertension and anemia were the most common adverse events. Conclusion: Lenvatinib may be a viable treatment option for mPPGL, although at the potential risk of worsening hypertension. Larger, multicenter studies are needed to better characterize treatment efficacy.