Prognostic risk factors of buccal squamous cell carcinoma: A case-control study.

OBJECTIVES: To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival. METHODS: This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review. RESULTS: Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors. CONCLUSIONS: Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar.

The neutrophil-to-lymphocyte ratio in salivary gland cancers treated with pembrolizumab.

BACKGROUND: A minority of patients with recurrent/metastatic (R/M) salivary gland cancers (SGCs) benefit from immune checkpoint inhibitors (ICIs), necessitating reliable biomarkers for ICI response prediction. METHODS: Retrospective observational study of R/M SGC patients treated with pembrolizumab between 2016 and 2022, with a primary outcome of 6-month progression-free survival (PFS) and secondary outcome of 2-year overall survival (OS). Univariate and multivariable Cox proportional hazards models were employed. RESULTS: Twenty R/M SGC patients were included. After adjustment, NLR as a continuous variable was independently associated with 6-month PFS (HR 1.30, 95% CI 1.10-1.54, p = 0.002) and 2-year OS (HR 1.33, 95% CI 1.07-1.66, p = 0.010). Similarly, NLR ≥ 5 was associated with higher hazards of progression at 6 months (HR 12.85, 95% CI 2.17-76.16, p = 0.005) and death at 2 years (HR 11.25, 95% CI 1.67-75.77, p = 0.013). CONCLUSIONS: Higher pretreatment NLR was independently associated with inferior 6-month PFS and 2-year OS in pembrolizumab-treated R/M SGC patients.

Bioinspired Total Synthesis of Hyperireflexolides A and B.

Hyperireflexolides A and B were synthesized in six steps via the dearomatization and fragmentation of a simple acylphloroglucinol starting material. The dearomatized acylphloroglucinol undergoes a sequence of oxidative radical cyclization, retro-Dieckmann fragmentation, stereodivergent intramolecular carbonyl-ene reactions, and final α-hydroxy-ß-diketone rearrangements to give the target natural products. This sequence is based on a biosynthetic proposal that claims the hyperireflexolides as highly rearranged polycyclic polyprenylated acylphloroglucinols (PPAPs), which is supported by the structural revision of hyperireflexolide B.

Patterns of Postoperative Trismus Following Mandibulectomy and Fibula Free Flap Reconstruction.

The factors that contribute to postoperative trismus after mandibulectomy and fibula free flap reconstruction (FFFR) are undefined. We retrospectively assessed postoperative trismus (defined as a maximum interincisal opening ≤35 mm) in 106 patients undergoing mandibulectomy with FFFR, employing logistic regression to identify risk factors associated with this sequela. The surgical indication was primary ablation in 64%, salvage for recurrence in 24%, and osteonecrosis in 12%. Forty-five percent of patients had existing preoperative trismus, and 58% of patients received adjuvant radiation/chemoradiation following surgery. The overall rates of postoperative trismus were 76% in the early postoperative period (≤3 months after surgery) and 67% in the late postoperative period (>6 months after surgery). Late postoperative trismus occurred more frequently in patients with ramus-involving vs. ramus-preserving posterior mandibulotomies (82% vs. 46%, p = 0.004). A ramus-involving mandibulotomy was the only variable significantly associated with trismus >6 months postoperatively on multivariable logistic regression (OR, 7.94; 95% CI, 1.85−33.97; p = 0.005). This work demonstrates that trismus is common after mandibulectomy and FFFR, and suggests that posterior mandibulotomies that involve or remove the ramus may predispose to a higher risk of persistent postoperative trismus.

Intramolecular Tricarbonyl-Ene Reactions and α-Hydroxy-ß-Diketone Rearrangements Inspired by the Biosynthesis of Polycyclic Polyprenylated Acylphloroglucinols.

Structurally unique natural products pose biosynthetic puzzles whose solution can inspire new chemical reactions. Herein, we propose a unified biosynthetic pathway towards some complex meroterpenoids-the hyperireflexolides, biyoulactones, hybeanones and hypermonones. This hypothesis led to the discovery of uncatalyzed, intramolecular carbonyl-ene reactions that are spontaneous at room temperature. We also developed an anionic cascade reaction featuring an α-hydroxy-ß-diketone rearrangement and an intramolecular aldol reaction to access four distinct natural product scaffolds from a common intermediate.

Biomimetic synthesis of the non-canonical PPAP natural products yezo'otogirin C and hypermogin D, and studies towards the synthesis of norascyronone A.

Oxidative degradation and rearrangement of polycyclic polyprenylated acylphloroglucinols (PPAPs) has created diverse families of unique natural products that are attractive targets for biomimetic synthesis. Herein, we report a racemic synthesis of hyperibrin A and its oxidative radical cyclization to give yezo'otogirin C, followed by epoxidation and House-Meinwald rearrangement to give hypermogin D. We also investigated the biomimetic synthesis of norascyronone A via a similar radical cyclization pathway, with unexpected results that give insight into its biosynthesis.

Adenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?

Adenosine deaminase (ADA) is a purine metabolism enzyme that catalyses the breakdown of adenosine and deoxyadenosine. The enzyme is important in several cellular processes, including the innate immune response and cellular differentiation, and it is also an important enzyme for the maintenance of brain homeostasis, in part due to its regulation of adenosine. Aberrant regulation of ADA enzyme activity has been linked to several neurodegenerative diseases and diseases that can result in neurological impairment. However, the mechanisms behind altered ADA regulation and how this leads to the development of neurological dysfunction are poorly characterised. This review summarises the current research on ADA and its role and regulation in disease pathology, with a focus on the central nervous system (CNS) and the neurodegenerative disease, amyotrophic lateral sclerosis (ALS).

Adjuvant therapy improves survival in pT4aN0 oral cavity squamous cell carcinoma with bone invasion.

OBJECTIVE: The prognostic significance of bone invasion in oral cavity squamous cell carcinoma (OCSCC) after accounting for tumor size, nodal spread, and surgical margins is controversial. The aim of this study is to determine whether patients with pT4aN0 oral cavity squamous cell carcinoma with bone invasion have improved overall and disease-free survival with adjuvant treatment. METHODS: We conducted a retrospective review of medical records from 64 patients with stage pT4aN0 due to mandibular involvement who underwent surgery from 2000 to 2020. Kaplan-Meier analysis compared disease-free survival and overall survival between groups who underwent surgery only versus surgery and adjuvant therapy. The prognostic impact of adjuvant therapy was assessed using multivariate analysis and reported as hazard ratios. RESULTS: There were no statistically significant differences in clinicopathologic features or mean follow-up between patients who received surgery only and patients who received surgery with RT/CCRT (radiotherapy/concurrent chemoradiation therapy). 5-year disease-free (42.5% versus 65.9%, p = 0.02) and overall survival (43.6% versus 69.0%, p = 0.014) were improved in groups who received surgery and RT/CCRT. Regression analysis controlling for clinicopathologic characteristics, including tumor size, identified radiation as an independent predictor of improved disease-free survival (HR: 0.04, p < 0.001) and overall survival (HR: 0.10, p < 0.001). CONCLUSION: Adjuvant RT/CCRT in patients with pT4N0 OCSCC with mandibular bone involvement is associated with improved disease-free and overall survival. This association was significant regardless of tumor pathologic features such as size or margin status. These findings may help guide physicians in counseling patients regarding risks and benefits of adjuvant RT/CCRT and inform practice guidelines.

Impact of Smoking and Primary Tumor Subsite on Recurrence in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To describe risk of recurrence and recurrence characteristics between ever- and never-smoking patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) when stratified by primary tumor subsite. STUDY DESIGN: Retrospective observational study. SETTING: Tertiary care center. METHODS: Retrospective chart review of 171 patients with HPV+ OPSCC with primary treatment between 2008 and 2019. Five-year recurrence-free survival and risk of recurrence were evaluated through Kaplan-Meier curves with log-rank test and Cox proportional hazards models, respectively. RESULTS: Of 171 patients with HPV+ OPSCC, 81.9% were male, and the average age was 63.9 years. Eighty patients (46.8%) had a smoking history (average, 17.7 pack-years), including 4 current smokers. Recurrence occurred in 31 patients (18.1%), 19 of whom were ever smokers. The recurrence rate for ever smokers with primary base of tongue (BOT) cancer was 41.7%, while 5.1% of never smokers with BOT primaries had recurrence. For primary tonsillar disease, 9.1% of ever smokers had recurrence versus 19.2% of never smokers. Five-year recurrence-free survival for BOT primaries was lower in ever smokers than never smokers (P = .001) but did not differ between ever and never smokers for tonsillar primaries (P = .215). In multivariable analysis across this period, ever-smoking status was associated with higher risk of recurrence than never-smoking status in BOT primaries (adjusted hazard ratio, 7.36; 95% CI, 1.61-33.68; P = .010) but with lower risk of recurrence after tonsillar primaries (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.89; P = .033). CONCLUSION: Smoking may uniquely interact with tumor subsites within the oropharynx to influence recurrence risk. Understanding the association between smoking and HPV+ OPSCC recurrence could lead to personalized, evidence-based treatments to improve oncologic outcomes.

Should Sentinel Lymph Node Biopsy Status Guide Adjuvant Radiation Therapy in Patients With Merkel Cell Carcinoma?

PURPOSE: Radiation of the draining lymph node basin remains controversial for Merkel cell carcinoma, particularly in the era of sentinel lymph node biopsy (SLNB). METHODS AND MATERIALS: Based on a 20-year experience using SLNB-guided adjuvant radiation therapy (RT), we conducted a retrospective review of clinically node-negative patients testing 2 hypotheses: (1) whether nodal RT could be safely omitted in SLNB-negative Merkel cell carcinoma and (2) whether the excised primary site should always be radiated. Clinically node-positive patients were excluded. RESULTS: Among 57 clinically node-negative patients who underwent SLNB and wide local excision (WLE), 42 (74%) had a negative SLNB, and 15 (26%) had a positive SLNB. At a median follow-up of 43 months (range, 5-182), SLNB-negative patients irradiated to the primary site had improved 4-year disease-specific survival (100% vs 65%, P = .008), local recurrence-free survival (100% vs 76%, P = .009), and distant recurrence-free survival (100% vs 75%, P = .008), but not overall survival (87.5% vs 57.7%, P = .164) compared with SLNB-positive patients receiving comprehensive RT. Among SLNB-negative patients treated with WLE only, 67% (6/9) had a disease relapse, half of which were local relapses (33%). CONCLUSIONS: In this single-institution retrospective review, after negative SLNB and WLE, RT given only to the primary site provided 100% disease control without a need for nodal RT. Among SLNB-negative patients who had WLE, omission of postoperative primary-site RT was associated with 67% cancer relapse, of which half was local.

Radiation treatment planning study to investigate feasibility of delivering Immunotherapy in Combination with Ablative Radiosurgery to Ultra-High DoSes (ICARUS).

PURPOSE: Immune checkpoint inhibitors improve survival in metastatic diseases for some cancers. Multisite SBRT with pembrolizumab (SBRT + Pembro) was shown to be safe with promising local control using biologically effective doses (BEDs) = 95-120 Gy. Increased BED may improve response rate; however, SBRT doses are limited by surrounding organs at risk (OARs). The purpose of this work was to develop and validate methods for safe delivery of ultra-high doses of radiation (BED10  > 300) to be used in future clinical trials. METHODS AND MATERIALS: The radiation plans from 15 patients enrolled on a phase I trial of SBRT + pembro were reanalyzed. Metastatic disease sites included liver (8/15), inguinal region (1/15), pelvis (2/15), lung (1/15), abdomen (1/15), spleen (1/15), and groin (1/15). Gross tumor volumes (GTVs) ranged from 80 to 708 cc. Following the same methodology used in the Phase I trial on which these patients were treated, GTVs > 65 cc were contracted to a 65 cc subvolume (SubGTV) resulting in only a portion of the GTV receiving prescription dose. Volumetric modulated arc therapy (VMAT) was used to plan treatments BED10  = 360 Gy. Plans utilizing both 6FFF and 10FFF beams were compared to clinical plans delivering BED10  = 112.50 Gy. The target primary goal was V100% > 95% with a secondary goal of V70% > 99% and OAR objectives per the trial. To demonstrate feasibility, plans were delivered to a diode array phantom and evaluated for fidelity using gamma analysis. RESULTS: All 30 plans met the secondary coverage goal and satisfied all OAR constraints. The primary goal was achieved in 12/15 of the 6FFF plans and 13/15 of the 10FFF plans. Average gamma analysis passing rate using criteria of 3% dose difference and 3, 2, and 1 mm were 99.1  ±  1.0%, 98.5  ±  1.6%, and 95.1  ±  3.8%, respectively. CONCLUSION: Novel VMAT planning approaches with clinical treatment planning software and linear accelerators prove capable of delivering radiation doses in excess of 360 Gy BED10 to tumor subvolumes, while maintaining safe OAR doses.

Patient-Reported Outcomes of Split-Thickness Skin Grafts for Floor of Mouth Cancer Reconstruction.

INTRODUCTION: Patient-reported outcome measures (PROM) on quality of life (QOL) for early-stage floor of mouth carcinoma (FOM-CA) undergoing surgical resection and split-thickness skin graft (STSG) reconstruction have not been established. We have performed a cross-sectional QOL analysis of such patients to define functional postoperative outcomes. METHODS: Patients with pathologic stage T1/T2 FOM-CA who underwent resection and STSG reconstruction at a tertiary academic cancer center reported outcomes with the University of Washington QOL (v4) questionnaire after at least 6 months since surgery. RESULTS: Twenty-four out of 49 eligible patients completed questionnaires with a mean follow-up of 41 months (range: 6-88). Subsites of tumor involvement/resection included the following: (1) lateral FOM (L-FOM) (n = 17), (2) anterior FOM (A-FOM) (n = 4), and (3) alveolar ridge with FOM, all of whom underwent lateral marginal mandibulectomy (MM-FOM) (n = 3). All patients reported swallowing scores of 70 ("I cannot swallow certain solid foods") or better. Ninety-six percent (23/24) reported speech of 70 ("difficulty saying some words, but I can be understood over the phone") or better. A-FOM patients reported worse chewing than L-FOM patients (mean: 50.0 vs. 85.3; p = 0.01). All 4 A-FOM patients reported a low chewing score of 50 ("I can eat soft solids but cannot chew some foods"). Otherwise, there were no significant differences between subsite groups in swallowing, speech, or taste. CONCLUSION: STSG reconstructions for pathologic T1-T2 FOM-CA appear to result in acceptable PROM QOL outcomes with the exception of A-FOM tumors having worse chewing outcomes.

Patient-Reported Quality of Life After Resection With Primary Closure for Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: For early-stage oral tongue carcinoma and carcinoma in situ (ESOTCCIS), we evaluated patient-reported quality-of-life (QOL) outcomes following resection with primary closure (R-PC). STUDY DESIGN: Retrospective review at an academic cancer center. METHODS: Thirty-nine ESOTCCIS patients (Tis, T1, T2) who underwent R-PC without radiation completed the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL) at least 6 months since R-PC (mean = 2.39 years; range = 0.5-6.7 years). We compared UW-QOL scores for pain, swallowing, chewing, speech, and taste to established normative population scores. Multivariable regression analysis evaluated factors associated with QOL impairment. RESULTS: ESOTCCIS patients who underwent R-PC in comparison to the normative population reported significantly worse mean speech (87.7 vs. 98, P < .001) and taste (85.6 vs. 95, P = .002) scores and no significant differences in mean pain (91.7 vs. 86, P = .96), swallowing (100 vs. 98, P = .98), chewing (97.4 vs. 94, P = .98) scores. For speech and taste, 59% (23/39) reported no postoperative change from baseline, whereas 41% (16/39) and 35.9% (14/39) reported mild impairment, respectively. Overall, postoperative QOL was reported as good, very good, or outstanding by 87.2% (34/39). Higher American Society of Anesthesiologists class, cT1 compared to CIS, and ventral tongue involvement were independently associated with worse speech. Age < 60 years was independently associated with worse taste. CONCLUSIONS: ESOTCCIS patients who undergo R-PC without radiation can expect long-term swallowing, chewing, and pain to be in the normative range. Although a majority of patients can expect to achieve normative speech and taste outcomes, R-PC carries the risks of mild speech and/or taste impairments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:312-318, 2021.

Head and neck surgery during the coronavirus-19 pandemic: The University of California San Francisco experience.

BACKGROUND: Guidelines regarding head and neck surgical care have evolved during the coronavirus-19 (COVID-19) pandemic. Data on operative management have been limited. METHODS: We compared two cohorts of patients undergoing head and neck or reconstructive surgery between March 16, 2019 and April 16, 2019 (pre-COVID-19) and March 16, 2020 and April 16, 2020 (COVID-19) at an academic center. Perioperative, intraoperative, and postoperative outcomes were recorded. RESULTS: There were 63 operations during COVID-19 and 84 operations during pre-COVID-19. During COVID-19, a smaller proportion of patients had benign pathology (12% vs 20%, respectively) and underwent thyroid procedures (2% vs 23%) while a greater proportion of patients underwent microvascular reconstruction±ablation (24% vs 12%,). Operative times increased, especially among patients undergoing microvascular reconstruction±ablation (687 ± 112 vs 596 ± 91 minutes, P = .04). Complication rates and length of stay were similar. CONCLUSIONS: During COVID-19, perioperative outcomes were similar, operative time increased, and there were no recorded transmissions to staff or patients. Continued surgical management of head and neck cancer patients can be provided safely.

Real-Time PCR and Droplet Digital PCR Are Accurate and Reliable Methods To Quantify Pseudomonas syringae pv. actinidiae Biovar 3 in Kiwifruit Infected Plantlets.

Pseudomonas syringae pv. actinidiae is the etiological agent of kiwifruit canker disease, causing severe economic losses in kiwifruit production areas around the world. Rapid diagnosis, understanding of bacterial virulence, and rate of infection in kiwifruit cultivars are important in applying effective measures of disease control. P. syringae pv. actinidiae load in kiwifruit is currently determined by a labor-intense colony counting method with no high-throughput and specific quantification method being validated. In this work, we used three alternative P. syringae pv. actinidiae quantification methods in two infected kiwifruit cultivars: start of growth time, quantitative PCR (qPCR), and droplet digital PCR (ddPCR). Method performance in each case was compared with the colony counting method. Methods were validated using calibration curves obtained with serial dilutions of P. syringae pv. actinidiae biovar 3 (Psa3) inoculum and standard growth curves obtained from kiwifruit samples infected with Psa3 inoculum. All three alternative methods showed high correlation (r > 0.85) with the colony counting method. qPCR and ddPCR were very specific, sensitive (5 × 102 CFU/cm2), highly correlated to each other (r = 0.955), and flexible, allowing for sample storage. The inclusion of a kiwifruit biomass marker increased the methods' accuracy. The qPCR method was efficient and allowed for high-throughput processing, and the ddPCR method showed highly accurate results but was more expensive and time consuming. While not ideal for high-throughput processing, ddPCR was useful in developing accurate standard curves for the qPCR method. The combination of the two methods is high-throughput, specific for Psa3 quantification, and useful for research studies (e.g., disease phenotyping and host-pathogen interactions).

Modified technique of submandibular gland transfer followed by intensity modulated radiotherapy to reduce xerostomia in head and neck cancer patients.

BACKGROUND: Xerostomia is one of the most common long-term adverse effects of radiotherapy for head and neck cancer patients. Contralateral submandibular gland transfer (SMG-T) before radiotherapy was shown to reduce xerostomia compared to pilocarpine. We sought to evaluate a modification of this surgery preserving the ipsilateral facial artery and vein to simplify the SMG-T. METHODS: Eighteen patients planned for head and neck intensity modulated radiotherapy to both necks were reviewed. Surgical complications were recorded. The grade of xerostomia was assessed after treatment completion. RESULTS: There were no minor or major complications resulting from the modified SMG-T. At 24.5-months follow up, the incidence of post-treatment moderate to severe xerostomia was 16.7%. No locoregional recurrence occurred. Only one patient had distant solitary lung metastasis. CONCLUSION: The modified SMG-T technique is a practical and effective method to reduce the dose of radiation to the contralateral SMG and limit post-treatment xerostomia.

Round Cell Sarcoma with EWSR1-PATZ1 Gene Fusion in the Neck: Case Report and Review of the Literature.

EWSR1-PATZ1 is a rare gene fusion recently recognized to occur in round and spindle cell sarcomas. To date, fewer than 20 cases have been described in the literature. However, no dedicated case reports have detailed its presentation in the head and neck region. We recently cared for a 52-year-old woman with an isolated, single right level 5A cervical mass. Excisional biopsy at an external hospital revealed pathology results consistent with EWSR1-PATZ1 polyphenotypic round and spindle cell sarcoma. The patient subsequently underwent surgical excision of the tumor and right neck lymph node dissection followed by adjuvant chemoradiation. Laryngoscope, 2020.

Machine Learning for Predicting Complications in Head and Neck Microvascular Free Tissue Transfer.

OBJECTIVES/HYPOTHESIS: Machine learning (ML) is a type of artificial intelligence wherein a computer learns patterns and associations between variables to correctly predict outcomes. The objectives of this study were to 1) use a ML platform to identify factors important in predicting surgical complications in patients undergoing head and neck free tissue transfer, and 2) compare ML outputs to traditionally employed logistic regression models. STUDY DESIGN: Retrospective cohort study. METHODS: Using a dataset of 364 consecutive patients who underwent head and neck microvascular free tissue transfer at a single institution, 14 clinicopathologic characteristics were analyzed using a supervised ML algorithm of ensemble decision trees to predict surgical complications. The relative importance values of each variable in the ML analysis were then compared to logistic regression models. RESULTS: There were 166 surgical complications, which included bleeding or hematoma in 30 patients (8.2%), fistulae in 25 patients (6.9%), and infection or dehiscence in 52 patients (14.4%). There were 59 take-backs (16.2%), and six total (1.6%) and five partial (1.4%) flap failures. ML models were able to correctly classify outcomes with an accuracy of 65% to 75%. Factors that were identified in ML analyses as most important for predicting complications included institutional experience, flap ischemia time, age, and smoking pack-years. In contrast, the significant factors most frequently identified in traditional logistic regression analyses were patient age (P = .03), flap type (P = .03), and primary site of reconstruction (P = .06). CONCLUSIONS: In this single-institution dataset, ML algorithms identified factors for predicting complications after free tissue transfer that were distinct from traditional regression models. LEVEL OF EVIDENCE: 2c Laryngoscope, 2020.

Treatment modality impact on quality of life for human papillomavirus-associated oropharynx cancer.

OBJECTIVES/HYPOTHESIS: Compare treatment-related quality of life (QOL) impact for early-stage human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC) patients. STUDY DESIGN: Retrospective cohort at a tertiary center. METHODS: Stage I (T0-2/N0-1) HPV+ OPSCC patients (n = 76) with pretreatment Karnofsky scores ≥80 reported QOL after surgery alone (n = 17, 22%), surgery with adjuvant radiation ± chemotherapy (S-a[C]XRT) (n = 23, 30%), or definitive radiation ± chemotherapy (d[C]XRT) (n = 36, 47%) with the University of Washington QOL version 4 (UW-QOL); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (EORTC QLQ-C30) and Head and Neck Module (EORTC QLQ-HN35); University of Michigan Xerostomia, and Neck Dissection Impairment Index questionnaires (median follow-up = 2.2 years, interquartile range = 1.0-4.2 years). Treatment adverse events and gastrostomy tube rates were assessed. RESULTS: Over 87% of each treatment group reported good or better overall QOL. Each group had low gastrostomy tube and treatment-specific complication rates. S-a(C)XRT and d(C)XRT patients had similar mean scores with wide ranges for most individual and all composite categories. S-a(C)XRT compared to d(C)XRT patients reported significantly fewer dental problems (EORTC QLQ-C30/HN35 means = 10.1 vs. 34.3, P = .007), worse appearance (UW-QOL means = 72.8 vs. 82.6, P = .02), and worse coughing (EORTC QLQ-C30/HN35 means = 31.9 vs. 15.7, P = .007). Surgery alone compared to d(C)XRT and S-a(C)XRT patients reported significantly better salivary/taste/oral functions and less pain, financial, oral/dental, and sexual problems. CONCLUSIONS: For early-stage HPV+ OPSCC, patients usually achieve acceptable QOL regardless of treatment. S-a(C)XRT and d(C)XRT patients report generally similar QOL including neck/shoulder pain/function, but with a wide range in a limited patient sample. Surgery alone should be considered, when oncologically and functionally safe, given the better associated QOL. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E48-E56, 2020.

Beyond Depth of Invasion: Adverse Pathologic Tumor Features in Early Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: In small (≤2 cm) oral tongue squamous cell carcinoma (OTSCC), we sought to clarify the contribution of pathologic features including perineural invasion (PNI), lymphovascular invasion (LVI), and worst pattern of invasion-5 (WPOI-5) to clinical outcomes relative to tumor depth of invasion (DOI) of > or ≤ 4 mm. METHODS: Cases of ≤2 cm OTSCC treated surgically between 2000 and 2017 at an academic cancer center were reviewed, with retrospective pathologic slide review of DOI, LVI, PNI, and WPOI-5. Primary outcome measures included occult nodal positivity, 2-year locoregional recurrence (LRR), disease-specific survival (DSS), and overall survival (OS). RESULTS: One hundred tumors were included in analyses; 50 had DOI ≤ 4 mm, while 50 had DOI > 4 mm. When DOI was ≤4 mm, the presence of PNI, LVI, or WPOI-5 was not associated with higher rates of occult cervical metastasis, LRR, or OS. When DOI was >4 mm, there was no difference in rates of occult cervical metastasis or LRR with each feature. On multivariate analysis, only the presence of two or more adverse features was associated with higher LRR (OR 5.7, P = .01) and worse DSS (HR 6.5, P = .02). CONCLUSION: The rate of occult cervical metastases in small (≤2 cm) OTSCC when DOI is ≤4 mm is very low even when PNI, LVI, or WPOI-5 is present, and 2-year LRR is no different. When DOI is >4 mm, the strongest predictor of recurrence and survival on multivariate analysis is the presence of two or more features in the tumor. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1715-1720, 2020.