Chintakuntlawar, Ashish V.

Head and neck cancer (HNC) accounted for 4% of all malignancies in 2022 and is often associated with tobacco and alcohol use, but the incidence of human papillomavirus (HPV)–associated HNC has steadily increased in recent decades. Unlike HPV-negative HNC, HPV-positive HNC has a favorable prognosis and survival is significantly better resulting in a large population of HNC survivors. Survivorship for HNC is of the utmost importance as there is a high burden of side effects that impact function and quality of life, and the patients with HPV HNC are living longer with the sequelae of their treatment.

AbstractBackgroundWe 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).MethodsRetrospective 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.ResultsAll 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).ConclusionsLower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.Level of Evidence3

ObjectiveFailure 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.MethodsRetrospective 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.ResultsOf 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.ConclusionsDelays 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 Evidence4 Laryngoscope, 133:1394–1401, 2023

TPS6111 Background: Treatment options for recurrent and/or metastatic (R/M) salivary gland cancer (SGC) are limited with response rates to standard cytotoxic chemotherapy (CT) low at 10-30%, and responses to single-agent immune checkpoint inhibition (ICI) <10%. Current therapeutic agents used to treat R/M SGC have an unfavorable toxicity profile including cytotoxic CTs such as cisplatin and doxorubicin and the targeted therapy lenvatinib. Treatments with general applicability and acceptable side effect profile are urgently needed. Pemetrexed (PTX) is a multi-targeted anti-folate CT with an excellent safety and toxicity profile with promising responses reported in a case series of patients (pts) with R/M SGC (Viscuse P and Price K. Marked responses to pemetrexed chemotherapy for metastatic adenocarcinoma of the parotid gland: case series. Head Neck 2019;41(6):E99-103.). As the combination of PTX and pembrolizumab (PMB) showed enhanced responses and survival in pts with lung cancer, we hypothesize that PTX and PMB will have efficacy in pts with R/M SGC and that the combination will have improved anti-cancer activity compared with historical controls. Correlative studies on archived tissues include methylthioadenosine phosphorylase loss, PDL1 expression, and thymidylate synthase expression as potential biomarkers of response. Methods: MC200708 is a single institution (3-site), open-label, single arm phase II study of PTX and PMB in patients with R/M SGC. Pts will be treated in two cohorts: one for pts with adenoid cystic carcinoma (ACC) and the other for pts with all other types of SGC (non-ACC cohort). Eligible pts must be ≥18 years old, have a pathologically confirmed SGC that is not amenable to curative-intent therapy, ECOG 0-2, adequate organ function, and at least 1 measurable lesion by RECIST 1.1. Any number of lines of prior therapy is allowed; prior treatment with checkpoint inhibitors and/or PTX is allowed. Key exclusion criteria: serious medical co-morbidity or autoimmune disease, prior grade 3-4 adverse event (AE) or grade 2-4 lung AE with ICI, and uncontrolled brain metastases. Simon’s two-stage design will be used for each cohort separately given the expected difference in responses in pts with ACC and non-ACC. Primary endpoint is overall response rate. Secondary endpoints are progression free and overall survival and toxicity. All patients will receive the same treatment of PTX 500 mg/m2 IV + PMB 200 mg IV every 3 weeks until disease progression or treatment intolerance. Response assessments will occur every 3 cycles. Enrollment began July 2021 and 16 of the planned 45 patients (ACC cohort 9 of 20 pts, non-ACC 7 of 25) have been accrued. Clinical trial information: NCT04895735.

AbstractObjectiveEsthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival.Materials and methodsWe performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression‐free survival (PFS), and distant metastasis–free survival (DMFS) were reported.ResultsAmong 143 included patients, the 5‐year OS was 82.3% and the 5‐year PFS was 51.6%; 5‐year OS and PFS have improved in the modern era (2005–present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p < 0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p < 0.05). Positive margin status had a negative effect on PFS (p < 0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p < 0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p < 0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p < 0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p < 0.05).ConclusionsPatients with low Hyams grade and mKadish stage have favorable 5‐year OS, PFS, and DMFS.

Abstract 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.

AbstractBackgroundThe development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence‐based statement on the definition of advanced thyroid cancer and its targeted systemic treatment.MethodsAn expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel.ResultsA review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided.ConclusionsWith the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted.

ObjectiveTo describe and compare rates of metachronous and synchronous second primaries of the contralateral tonsil in patients with primary HPV(+) tonsillar squamous cell carcinoma (SCC).Study DesignRetrospective cohort study.Materials and MethodsThis is a single tertiary care center retrospective case series, from 2006 to 2019, of HPV(+) tonsillar SCC patients who underwent primary surgical resection with unilateral wide‐field tonsillectomy or bilateral tonsillectomy for diagnostic or therapeutic purposes. A metachronous second primary is one diagnosed >6 months after completion of surgical treatment. A synchronous second primary is one diagnosed during bilateral tonsillectomy for unilateral HPV(+) tonsillar SCC. Rates of second primary and patient characteristics were compared using chi‐square tests.ResultsAbout 303 patients underwent unilateral surgical resection +/− adjuvant therapy for HPV(+) tonsillar SCC. One (0.3%) developed a metachronous second primary in the contralateral tonsil 11.9 years following treatment. Fifty‐seven patients with HPV(+) tonsillar SCC underwent bilateral tonsillectomy, and 37/57 (65%) had no clinical signs for contralateral disease. Of these, only 1/37 (2.7%) was incidentally found to have a synchronous second primary. Twenty patients underwent bilateral tonsillectomy due to clinical concern for contralateral disease. Of these, 3/20 (15%) were found to have a synchronous HPV(+) SCC in the contralateral tonsil.ConclusionsThe prevalence of metachronous second primary after appropriate treatment of HPV(+) tonsillar SCC is very low (0.3%) and so is the chance of incidentally discovering a synchronous second primary during bilateral tonsillectomy (2.7%). We do not recommend bilateral tonsillectomy as a part of the routine algorithm in the surgical management of these patients.Level of Evidence3 Laryngoscope, 132:332–338, 2022