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Background: Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC). Methods: From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent. Multivariable Cox regression was used to relate patient/treatment characteristics with disease‐free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable. Results: A total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72–1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70–1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87–1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83–1.11, p = 0.58). Conclusion: No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC. [ABSTRACT FROM AUTHOR]

Objective: Organ preservation (OP) treatment for advanced laryngeal cancer has increased compared to primary total laryngectomy. Our study compares oncologic and functional outcomes between these approaches. Study Design: Retrospective cohort study. Setting: Single tertiary care institution. Methods: Retrospective review of patients receiving primary total laryngectomy or OP for laryngeal cancer between 1/1/2000 and 12/31/2018. Results: A total of 118 patients received primary total laryngectomy and 119 received OP. Overall survival was similar between total laryngectomy and OP. When stratified by T stage, disease‐free survival was worse among T3 patients receiving OP versus total laryngectomy. In T3 patients, 28 OP patients experienced local recurrence (28.9%) compared to 3 total laryngectomy patients (7.1%; p < 0.01). In total, 20 OP patients with local recurrence received salvage surgery. These patients had similar overall survival to patients who underwent initial total laryngectomy (TL). About 14 OP patients with local recurrence did not receive salvage surgery. About 89 (75.4%) TL patients achieved normal diet as compared to 64 (53.8%) OP patients (p < 0.001). In TL patients, 106 (89.8%) received primary or secondary tracheoesophageal‐prosthesis, 82 (77.4%) of whom achieved completely understandable speech. Conclusions: There was no difference in survival by treatment in T4 patients, possibly because of strict patient selection. However, disease‐free survival was worse in T3 patients receiving OP, likely due to a high local recurrence rate. Approximately 40% of patients with local recurrence were not eligible for salvage laryngectomy. TL patients had comparable swallowing and speech outcomes with OP patients. Level of Evidence: 3 Laryngoscope, 133:1122–1131, 2023 [ABSTRACT FROM AUTHOR]

Objectives: Evaluate outcomes of patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy (IO). Methods: Among patients with R/M HNSCC treated with IO in this retrospective single‐institution cohort, Cox regression was used to compare overall survival (OS) for those with platinum‐refractory disease and those treated in the first‐line setting with OS from KEYNOTE‐040/048, respectively. Multivariable Cox regression was used to identify predictors of OS. Results: There was no significant OS difference for those treated in the platinum‐refractory setting when compared to patients on KEYNOTE‐040 (HR = 1.22, p = 0.27), nor for the first‐line setting compared to KEYNOTE‐048 (HR = 1.23, p = 0.19). ECOG‐PS 1 (HR = 2.00, p = 0.02) and ECOG‐PS 2 (HR = 3.13, p < 0.01) were associated with worse OS. Higher absolute lymphocyte count (ALC) was associated with improved OS (HR = 0.93 per 100 cells/μL, p = 0.03). Conclusions: Real‐world outcomes of IO in R/M HNSCC are similar to outcomes in randomized control trials, with performance status and ALC correlating with OS. [ABSTRACT FROM AUTHOR]

Background: We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy. Methods: Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis. Results: Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease‐free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS. Conclusion: Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity. [ABSTRACT FROM AUTHOR]

Background: The 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. Methods: An 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. Results: A 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. Conclusions: With 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. [ABSTRACT FROM AUTHOR]

Background: The prognostication of Epstein–Barr virus (EBV) and human papillomavirus (HPV) status in nasopharyngeal cancer (NPC) is unclear. Methods: This retrospective study analyzed NPC from 2000 to 2019. Results: Seventy‐eight patients were included: 43 EBV+, 12 HPV+, 23 EBV−/HPV−, and 0 EBV+/HPV+. All p16+ tumors were also positive for HPV‐CISH. Baseline characteristics were not different between groups except age, N‐classification, and Karnofsky Performance Scale (KPS) (p < 0.05). For EBV+, HPV+, and EBV−/HPV− respectively, 3‐year overall survival (OS) was 89.9%, 69.8%, and 52.5% (p = 0.006). EBV−/HPV− status was significantly associated with worse OS but not freedom from progression (FFP) on univariate analysis, and did not remain a significant predictor of OS after adjusting for KPS, age, and group stage. Conclusions: EBV+ NPC tumors were seen in younger, healthier patients than HPV+ and EBV− tumors, and there were no cases of coinfection. The association of viral status with OS was insignificant after adjusting for KPS and age. [ABSTRACT FROM AUTHOR]

Standard of care for high‐risk cutaneous squamous cell carcinoma (cSCC) is surgical excision of the primary lesion with clear margins when possible, and additional resection of positive margins when feasible. Even with negative margins, certain high‐risk factors warrant consideration of adjuvant therapy. However, which patients might benefit from adjuvant therapy is unclear, and supporting evidence is conflicting and limited to mostly small retrospective cohorts. Here, we review literature from the last decade regarding adjuvant radiation therapy and systemic therapy in high‐risk cSCC, including recent and current trials and the role of immune checkpoint inhibitors. We demonstrate evidence gaps in adjuvant therapy for high‐risk cSCC and the need for prognostic tools, such as gene expression profiling, to guide patient selection. More large‐cohort clinical studies are needed for collecting high‐quality, evidence‐based data for determining which patients with high‐risk cSCC may benefit from adjuvant therapy and which therapy is most appropriate for patient management. [ABSTRACT FROM AUTHOR]

Objective: Buccal cells are an ideal surrogate tissue for studying biologic effects of carcinogens or drugs, however inherent fragility and salivary RNAses limit RNA yield. We conducted healthy volunteer trials to optimize collection conditions. Methods: We conducted: (a) a single‐arm crossover study evaluating four test conditions on RNA yield by buccal cytobrush; (b) a single‐arm prospective study evaluating RNA yield by investigator vs self‐collection. Results: Antecedent toothbrushing, time of day, and number of cytobrush strokes did not significantly impact RNA yield. RNA yield was doubled by using 2 vs 1 cytobrush per buccal surface (P =.0054). Self‐collection of buccal cells for RNA was feasible; 36 of 50 (72%) samples passed quality control. Conclusion: RNA yield was doubled by using two cytobrushes per buccal surface. Healthy volunteers can self‐collect sufficient buccal RNA for gene expression studies. Techniques from these pragmatic trials could enhance availability of a limited tissue for serial biomarker measurements. Level of Evidence: 1b—Prognosis Study (Individual prospective cohort study). [ABSTRACT FROM AUTHOR]

Background: Process‐related measures have been proposed as quality metrics in head and neck cancer care. A recent single‐institution study identified four key metrics associated with increased survival. This study sought to validate the association of these quality metrics with survival in a multi‐institutional cohort. Methods: Multicenter retrospective study of patients with oral cavity squamous cell (1/2005‐1/2015). Baseline patient and disease characteristics and compliance with quality metrics was evaluated. Association between compliance with quality metrics with overall survival (OS), disease‐free survival (DFS), and disease‐specific survival (DSS) was evaluated using Cox proportional hazards models. Results: Failure to comply with two or more of the quality metrics was associated with worse OS, DFS, and DSS. Adherence to all or all but one of the quality metrics was found to be associated with improved survival. Conclusions: Process‐related quality metrics are associated with increased survival in patients with oral cavity squamous cell carcinoma in a multi‐institutional cohort. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between tumor volume and locoregional failure (LRF) after concurrent chemoradiation (CCRT) for locally advanced larynx cancer (LC).Methods: This is a retrospective cohort study from 2009 to 2014 identified from an institutional review board-approved registry. Fifty-nine of 68 patients with locally advanced larynx cancer treated with definitive CCRT who had available imaging for review were identified. The main endpoint to be assessed was the association between gross tumor volumes (GTV; T = total, P = primary, N = nodal) and LRF. Receiver operative characteristic (ROC) curves were used to investigate diagnostic accuracy.Results: Twenty LRFs were observed, resulting in a 2-year LRF rate of 39% (95% CI, 23-52%). On UVA, the GTV-T (P = .01), GTV-P (P = .05), and GTV-N (P = .04) were statistically significant predictors of LRF. Furthermore, age, smoking status, N-stage, larynx subsite, and tracheostomy/feeding tube dependence were potentially associated with LRF (P < .3), whereas T-stage (T3-4 vs. T2) was not (HR 1.05, 95% CI, 0.38-2.91, P = .92). In the multivariable model, GTV-P (HR 1.022, 95% CI, 0.999-1.046, P = .07) and GTV-N (HR 1.053, 95% CI, 1.0004-1.108, P = .05) were the two most impactful covariates on the model's R2 . ROC analysis suggested an optimal cut point of 12 cc in the GTV-T. The 2-year LRF for GTV-T > 12 cc was 64.2% and ≤ 12 cc was 16.4%, P = .006.Conclusion: GTV is associated with LRF after definitive CCRT for LC. Patients with bulky primary and/or nodal tumors may be better served with upfront surgical resection regardless of T-stage. Further investigation into the safety of larynx preservation for low-volume T4 tumors can be considered.Level Of Evidence: 4 Laryngoscope, 130:2372-2377, 2020. [ABSTRACT FROM AUTHOR]

Background: De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack-years may experience favorable outcomes if smoking cessation has been achieved.Methods: From an institutional review board-approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de-intensification trials were included (cT1-2N1-2b or T3N0-2b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack-years and time since cessation).Results: Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers, 139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression-free survival (PFS) rate higher than 91%, regardless of pack-year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with ≤20 pack-years. RPA demonstrated that only current smokers experienced a 2-year PFS rate lower than 91%; former smokers, regardless of pack-years, experienced a 2-year PFS rate higher than 91%.Conclusions: The 10-pack-year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de-intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established. [ABSTRACT FROM AUTHOR]

Background: The role of smoking among patients with human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is unclear. Methods: A retrospective cohort study of patients with HPV(+) OPSCC from 2001 to 2015 at a tertiary‐care institution was conducted. The primary outcome was overall survival (OS). Results: Among 484 included patients, 94 (19.4%) were active smokers, 226 (46.7%) were former smokers, and 164 (33.9%) never smoked. Among active smokers, 82 patients (87.2%) had a ≥10 pack‐year and 69 (73.4%) had a ≥20 pack‐year smoking history. After adjusting for covariates, active smoking was a significant predictor of inferior OS (HR 2.28, P <.001) and PFS (HR 2.26, P <.001). When including pack‐years as the covariate, ≥20 pack‐years predicted a decreased effect‐size for inferior OS and PFS. Conclusions: For patients with HPV(+) OPSCC, active smoking at diagnosis is the most powerful covariate capturing smoking history to predict OS and PFS. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Patients with human papillomavirus (HPV)-induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched-pair analysis to compare outcomes between T0N1-3M0 HPV+ CUP and T1-2N1-3M0 HPV+ oropharynx known primary (OPX).Study Design: Retrospective cohort study at a single institution.Methods: Patients with early T stage, node positive HPV+ OPX or CUP treated with curative intent between 1998 and 2016 were identified. For a subgroup of CUP patients with an unknown HPV status, we imputed HPV status and included patients with a >80% probability of being HPV+. Cohorts were matched based on patient demographics using a nearest neighbor propensity technique. After matching, patients were grouped according to either a favorable or unfavorable risk stratification designations per current NRG Oncology clinical trial enrollment criteria. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier analysis.Results: Of 298 patients with T1-2N1-3 OPX, 48 were matched to 48 HPV+ CUP patients (32 with confirmed and 16 imputed HPV status). Median follow-up for CUP (34.1 months) and OPX (27.8 months) patients were similar (P = .23).There were no significant differences between the CUP and OPX groups for 3-year DFS (89% vs. 85%, P = .44), and 3-year OS (91% vs. 91%, P = .11), respectively.Conclusions: Patients with T0N+M0 HPV-induced CUP have similar survival outcomes to matched patients with T1-2N+M0 HPV+ OPX. These patients can reasonably be included in clinical trials investigating the role of treatment deintensification and risk stratified similar to patients with early-stage known primary OPX cancer.Level Of Evidence: 4. Laryngoscope, 128:1379-1385, 2018. [ABSTRACT FROM AUTHOR]

Background Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. Methods This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. Results Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. Conclusion Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016 [ABSTRACT FROM AUTHOR]