A radiation therapy contouring atlas for delineation of the level I-II axilla in the prone position: a single institution experience.

PURPOSE: With transition from supine to prone, tenting of the pectoralis major occurs displacing the muscle from the chest wall and shifting the level I-II axillary spaces. For patients whom we aim to treat the level I-II axilla using the prone technique, accurate delineation of these nodal regions is necessary. While different consensus guidelines exist for delineation of nodal anatomy supine, to our knowledge there are no contouring guidelines in the prone position that account for this change in nodal anatomy. METHODS AND MATERIALS: The level I-II nodal contours from the Radiation Therapy Oncology Group (RTOG) breast cancer supine atlas were adapted for prone position by two radiation oncologists and a breast radiologist based on anatomic changes observed from supine to prone positioning on preoperative diagnostic imaging. Forty-three patients from a single institution treated with prone high tangents from 2012 to 2018 were identified as representative cases to delineate the revised level I-II axilla on non-contrast computed tomography (CT) scans obtained during radiation simulation. The revised nodal contours were reviewed by an expanded expert multidisciplinary panel including breast radiologists, radiation oncologists, and surgical oncologists for consistency and reproducibility. RESULTS: Consensus was achieved among the panel in order to create modifications from the RTOG breast atlas for CT-based contouring of the level I-II axilla prone using bone, muscle and skin as landmarks. This atlas provides representative examples and accompanying descriptions for the changes described to the caudal and anterior border of level II, and the anterior, posterior, medial and lateral border of level I. A step-by-step guide is provided for properly identifying the revised anterior border of the level I axilla. CONCLUSIONS: The adaptations to the RTOG breast cancer atlas for prone positioning will enable radiation oncologists to more accurately target the level I-II axilla when the axilla is a target in addition to the breast.

High-volume prostate biopsy core involvement is not associated with an increased risk of cancer recurrence following 5-fraction stereotactic body radiation therapy monotherapy.

PURPOSE: Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS: A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS: From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS: With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

Adjuvant Radiotherapy in Moderately Advanced (T3) Oral Cavity Cancers.

OBJECTIVE: To investigate the impact of adjuvant radiotherapy in isolated locally advanced oral cavity cancers (pT3N0M0) without adverse features. METHODS: We selected all patients from the National Cancer Database (2004-2019) who underwent surgical treatment where the final pathology was T3N0M0 with negative margins. Demographics, details of treatment, and outcomes were abstracted. The impact of radiotherapy on survival was assessed with univariable, multivariable, and propensity score-matched analyses. RESULTS: We identified 571 patients in our survival cohort. Most were male (348, 60.9%), and median age was 65. Less than one-third (176, 30.8%) received adjuvant radiotherapy. The median length of follow-up was 29 months. Overall, adjuvant radiotherapy was associated with improved survival (87.2% vs. 77.7%, at 2 years, p < 0.01). On multivariable analysis controlling for age and comorbidities, this survival difference persisted (HR: 0.62, 95% CI: 0.43-0.90, p = 0.01). In a propensity score-matched population of 278 patients matched on age and comorbidities, adjuvant radiotherapy was still associated with longer survival (87.4% vs. 78.5%, p = 0.014). CONCLUSION: In our study, adjuvant radiotherapy was associated with improved survival in completely excised locally advanced oral cavity tumors (T3N0M0). However, a significant proportion of patients do not receive adjuvant radiotherapy. These findings highlight the need for continued efforts to promote guideline-recommended care. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2236-2242, 2024.

Stereotactic Body Radiation Therapy for the Curative Treatment of Prostate Cancer in Ultralarge (≥100 cc) Glands.

PURPOSE: Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS: We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS: Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS: With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.

Pathologic Features, Treatment, and Clinical Outcomes of Lacrimal Gland Cancer.

OBJECTIVES: Lacrimal gland cancer is a rare malignancy with little data known about its pathologic characteristics or optimal management. We performed a large database analysis using the National Cancer Database (NCDB) to elucidate this unusual condition. METHODS: Patients with lacrimal gland cancer diagnosed between 2004 and 2018 were included in the analysis. Using available clinical data, we excluded all patients with histologies likely reflective of lacrimal sac or duct cancer, which are coded similarly to lacrimal gland cancer in the NCDB. Kaplan-Meier analysis was used to estimate overall survival (OS), and Cox proportional hazards models were used to indicate covariates associated with survival. RESULTS: A total of 440 cases of lacrimal gland cancer were included in the analysis, with a median follow-up of 52.9 months. The five-year OS for the entire cohort was 65.0%. Adenoid cystic carcinoma was the predominant histology (47.3%). Cox models showed that improved OS was associated with surgical resection (UVA: p < 0.001; MVA: p = 0.035). A detriment in OS was associated with increasing age, Charlson-Deyo score of 1, T4 stage, and positive margins and on UVA for adenocarcinoma and malignant mixed tumor histology. CONCLUSION: Adenoid cystic carcinoma comprises the plurality of lacrimal gland cancers. About half of patients with lacrimal gland carcinoma will live beyond 10 years, underscoring the importance of reduced morbidity of treatment. Surgical management is associated with improved prognosis. Further study will elucidate the role of surgical excision and radiotherapy in lacrimal gland cancer.

Stereotactic Body Radiation Therapy versus Surgical Resection for Stage I/II Hepatocellular Carcinoma.

SBRT is an emerging locoregional treatment modality for hepatocellular carcinoma (HCC). Although local tumor control rates seem encouraging, large-scale survival data comparing SBRT to surgical resection are lacking. We identified patients with stage I/II HCC from the National Cancer Database amenable for potential surgical resection. Patients undergoing hepatectomy were matched by propensity score (1:2) with patients who underwent SBRT as primary treatment. A total of 3787 (91%) and 366 (9%) patients underwent surgical resection or SBRT between 2004 and 2015, respectively. After propensity matching, the 5-year overall survival was 24% (95% CI 19-30%) in the SBRT group versus 48% (95% CI 43-53%) in the surgery group (p < 0.001). The association of surgery with overall survival was consistent in all subgroups. In patients treated with SBRT, a biologic effective dose (BED) of ≥100 Gy (31%, 95% CI 22%-40%) compared with BED < 100 Gy (13%, 95% CI 8-22%) was associated with a higher 5-year overall survival rate (hazard ratio of mortality of 0.58, 95% CI 0.43-0.77; p < 0.001). Surgical resection may be associated with prolonged overall survival compared with SBRT in patients with stage I/II HCC.

Surgical Treatment in Very Advanced (T4b) Adenoid Cystic Carcinoma of the Head and Neck.

OBJECTIVE: To compare treatment outcomes for T4b head and neck adenoid cystic carcinoma (ACC). STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database (NCDB). METHODS: Identified all T4b ACC of head and neck origin diagnosed 2004 to 2019 in the NCDB. Demographics, clinical characteristics, treatment details, and survival were analyzed. Treatment outcomes were analyzed using univariable and multivariable Cox regression. RESULTS: We identified 606 cases of T4b ACC. Less than half (284, 47.0%) underwent curative-intent treatment. Among these, most were treated with primary surgery: surgery + radiotherapy (RT) (122, 43.0%) or surgery + chemoradiotherapy (CRT) (42, 14.8%). The positive margin rate was 78.7%, and 90-day postoperative mortality was zero. Nonsurgical patients were treated with definitive RT (60, 21.1%) or definitive CRT (60, 21.1%). The median follow-up was 51.5 months. Overall survival was 77.8% at 3 years. Three-year survival was higher for patients treated with surgery compared to those treated nonsurgically (84% vs 70%; p = .005). Surgical treatment remained associated with higher survival on multivariable analysis (hazard ratio [HR]: 0.47, p = .005). This effect was most pronounced for oral cavity tumors (HR: 0.17, p = .01). Among matched cohorts of surgically treated patients, there was no difference in 3-year survival between clinical T4a and T4b tumors (83.3% vs 83.0%, p = .99). CONCLUSION: Long-term survival for T4b ACC of the head and neck could be expected. Primary surgical treatments can be performed safely and are associated with longer survival. A carefully selected subset of patients with very advanced ACC might benefit from the consideration of surgical treatments.

Repeat re-irradiation with interstitial HDR-brachytherapy for an in-field isolated nodal recurrence in a patient with HPV-positive squamous cell carcinoma of the head and neck.

PURPOSE: Locoregionally recurrent head and neck cancer is a complex clinical scenario that often requires multimodality treatment. These patients have often previously received definitive treatment with a combination of surgery, radiation therapy, and systemic therapy, which can make further management difficult. A second isolated locoregional failure is rare and clinicians are faced with a challenge to optimize disease control while minimizing treatment-related toxicity. METHODS AND MATERIALS: In this report, we present the diagnosis, management, and outcomes of a patient with an isolated locoregional recurrence who was previously treated with two courses of radiation. The patient was treated with a second course of reirradiation using interstitial brachytherapy as well as a discussion regarding patient selection and optimal management for recurrent head and neck cancer. RESULTS: Repeat reirradiation using interstitial HDR-brachytherapy with the use of an alloderm spacer was successfully delivered to the patient for an in-field right neck nodal recurrence. He received a total EQD2/BED dose of 127.70/153.24 Gy. At 1-year followup, the patient was without evidence of recurrent disease or new significant side effects. CONCLUSION: Recurrent head and neck cancer should be managed with a multidisciplinary approach given the complex clinical scenario. Reirradiation is a commonly used salvage measure for recurrent head and neck cancer that requires careful planning and patient selection due to prior treatment-related effects and dose constraints. We reported a case of a second course of reirradiation using interstitial HDR-brachytherapy for locoregionally recurrent head and neck cancer and showed no recurrence of disease or worsening long term side effects at 1 year.

Adoption of adjuvant chemotherapy in high-risk salivary gland malignancies.

BACKGROUND: The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies. METHODS: The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004-2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan-Meier analysis (HR: 0.98; 95% CI: 0.86-1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78-1.09; p = 0.34). CONCLUSIONS: Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

Patterns of Care and Outcomes of Carcinosarcoma of the Major Salivary Glands.

OBJECTIVE: Carcinosarcoma of the salivary gland is a rare malignant biphasic tumor. The present study investigates the epidemiology and clinical behavior of carcinosarcoma of the major salivary glands using the National Cancer Database (NCDB). STUDY DESIGN: Historical cohort study. SETTING: NCDB. METHODS: All tumors were selected between 2004 and 2018. Patient demographics, tumor characteristics, treatments, and survival were analyzed. Cox regression analysis was performed in surgically treated patients. RESULTS: We identified 154 patients in the NCDB with carcinosarcoma of the salivary gland. Median age at diagnosis was 66 years (interquartile range, 55-76). Most patients were male (n = 92, 60%). The majority of tumors were in the parotid (n = 122, 79%), followed by submandibular gland (n = 21, 14%). The majority were high grade (n = 93, 95%), and a significant portion had locally advanced disease (pT3-4; n = 65, 62%). Nodal disease was present in more than one-third (n = 35, 36%). The most common treatment was surgery with adjuvant radiotherapy (n = 75, 49%). With a median follow-up of 36 months, the 3-year overall survival was 57.6% (95% CI, 48.7%-68.0%). In univariable analysis, advanced pT stage, pN+ disease, and positive margins were associated with worse survival. In multivariable analysis, age (hazard ratio, 1.02; 95% CI, 1.01-1.04; P = .03) and pT stage (hazard ratio, 2.51; 95% CI, 1.27-4.95; P = .008) remained significant. CONCLUSION: Carcinosarcoma is a rare salivary gland tumor that frequently presents at a locally advanced stage. Despite multimodality treatments, the outcomes are poor. In the absence of clinical trial data, these data from the NCDB could guide clinicians in the management of this rare disease.

Nodal Metastases in Pediatric and Adult Acinic Cell Carcinoma of the Major Salivary Glands.

OBJECTIVE: Acinic cell carcinoma (AciCC) is a rare, usually low-grade salivary malignancy. Evidence on rates of lymph node metastases (LNMs) is limited in pediatric patients and varies significantly (4%-45%) in adults. We set out to determine and compare rates of LNMs in pediatric and adult AciCC and to analyze their impact on survival, using the National Cancer Database. STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database. METHODS: All AciCCs of the major salivary glands with complete clinical and pathologic nodal staging were selected between 2010 and 2016. Patient demographics, tumor characteristics, treatment, and survival were analyzed. Univariable and multivariable regression were performed to determine factors associated with LNMs and survival. RESULTS: We identified 57 (4.6%) pediatric patients (<18 years) and 1192 (95.4%) adults with AciCC. Clinical LNMs were rare in pediatric patients (n < 10) and adults (n = 88, 7.4%). Occult LNMs were uncommon in pediatric patients (n < 5) and adults (n = 41, 4.6%). Three-year overall survival for pediatric patients was 97.8%. Adults with LNM had worse 3-year overall survival than those without (66.0% vs 96.3%, P < .001). In multivariable regression, high-grade disease (hazard ratio, 10.15 [95% CI, 5.60-18.80]; P < .001) and T3-T4 tumors (hazard ratio, 2.80 [95% CI, 1.56-4.97]; P < .001) were associated with LNM in adult patients. CONCLUSION: LNMs in AciCC of the major salivary glands are rare in children and adults. However, high-grade and T3-T4 tumors are associated with an increased risk of LNM. LNM is associated with worse survival.

Non-Squamous Cell Malignancies of the Larynx.

OBJECTIVES/HYPOTHESIS: Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied. STUDY DESIGN: Retrospective cohort study. METHODS: Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients. RESULTS: A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001). CONCLUSION: A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1771-1777, 2022.

Human Papillomavirus in Patients With Hypopharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Assess the testing rates and prognostic significance of human papilloma virus (HPV) status in hypopharynx malignancies. STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database. METHODS: Review of the National Cancer Database was conducted between 2010 and 2017 for squamous cell carcinomas (SCCs) of the hypopharynx. We investigated how often the tumors were tested for HPV and whether it was associated with survival outcomes. RESULTS: A total of 13,269 patients with hypopharynx malignancies were identified. Most cases were not tested for HPV status (n = 8702, 65.6%). Of those tested, 872 (19.1%) were positive for HPV and 3695 (80.9%) were negative. The proportion of nonoropharyngeal SCCs tested for HPV increased nearly every year during the study, with roughly one-third of cases (31.9%) being tested in 2017. In the facilities classified as high-testing centers of nonoropharyngeal SCCs of the head and neck, 18.7% of hypopharyngeal tumors were HPV positive. HPV-negative status was associated with worse survival on multivariable analysis. In propensity score-matched analysis controlling for all factors significant in multivariable regression, 2-year survival remained higher in the HPV-positive cohort (77.7% vs 63.1%, P < .001). CONCLUSIONS: HPV-positive tumors constitute a sizable minority of hypopharynx tumors and are associated with improved survival. Expansion of HPV testing to hypopharynx malignancies may be warranted.

Including Surgical Resection in the Multimodal Management of Very Locally Advanced Sinonasal Cancer.

OBJECTIVE: Sinonasal cancer often presents as locoregionally advanced disease. National guidelines recommend management of stage T4b tumors with systemic therapy and radiotherapy, but recent studies suggest that including surgical resection in the multimodal treatment of these tumors may improve local control and survival. We queried the National Cancer Database to examine patterns of care and outcomes in T4b sinonasal squamous cell carcinoma (SCC). STUDY DESIGN: Prospectively gathered data. SETTING: National Cancer Database. METHODS: Patients with T4b N0-3 M0 sinonasal squamous cell carcinoma diagnosed in 2004 to 2016 were stratified between those who received chemoradiotherapy and those who underwent surgical resection with neoadjuvant or adjuvant treatment. The overall survival of each cohort was assessed via Kaplan-Meier analysis and Cox proportional hazard models, with repeat analysis after reweighting of data via inverse probability of treatment weighting. RESULTS: Among 805 patients included in analysis, 2-year overall survival for patients undergoing surgical resection was 60.8% (95% CI, 56.1%-65.9%), while for patients undergoing chemoradiotherapy it was 46.7% (95% CI, 41.9%-52.0%). On Cox regression analysis, the inclusion of surgery in management was associated with improved survival in univariate analysis (hazard ratio [HR], 0.723 [95% CI, 0.606-0.862]; P < .001) and multivariate analysis (HR, 0.739 [95% CI, 0.618-0.885]; P = .001). Results with reweighted data were consistent in univariate analysis (HR, 0.765 [95% CI, 0.636-0.920]; P = .004]). CONCLUSION: Surgical treatment with neoadjuvant or adjuvant treatment for stage T4b sinonasal SCC was associated with promising survival outcomes, suggesting a role for incorporating surgery in treatment of select T4b SCC, particularly when removal of all macroscopic disease is feasible.

Primary Surgical Treatment in Very Advanced (T4b) Oral Cavity Squamous Cell Carcinomas.

OBJECTIVES: To describe patterns of primary surgical treatments in patients with T4b oral cavity squamous cell carcinoma (OCSCC). STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database. METHODS: Review of the National Cancer Database between 2004 and 2017 for all T4b OCSCCs. Only patients with curative treatment methods were included in the survival analysis. Surgical and nonsurgical outcomes were compared by multivariable and propensity score matching analysis. RESULTS: A total of 1515 cases of T4b OCSCC were identified. A minority of patients (n = 363, 24.0%) underwent curative treatment; among these, 206 (56.7%) underwent primary surgery. Median length of follow-up was 24 months. The 90-day mortality of patients who underwent surgical treatment was 1.0%. The 2-year survival was higher for patients who underwent surgery + chemoradiotherapy (CRT) as compared with CRT (64.6% vs 45.2%, P < .001). On multivariable analysis, surgery + CRT was associated with longer survival. In a propensity score-matched cohort of 312 patients, 2-year survival remained higher in the surgical group versus the nonsurgical group (59.4% vs 45.5%, P = .02). Among patients who underwent surgery + CRT, there was no difference in 2-year survival between clinical T4a and T4b (59% vs 64.6%, P = .20). CONCLUSIONS: A minority of patients with T4b OCSCC undergo treatments with curative intent. A subset of patients underwent primary surgical treatment, which was associated with longer survival. The T4b classification might entail a heterogenous group, and further studies in revision of this classification might be justified.

Improved survival in women versus men with merkel cell carcinoma.

BACKGROUND: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies. OBJECTIVE: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC). METHODS: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality. RESULTS: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients. LIMITATIONS: Potential selection bias from a retrospective data set. CONCLUSION: In MCC, women have improved survival compared with men, driven by MCC-related mortality.

Socioeconomic and Racial Disparities and Survival of Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB). STUDY DESIGN: Population-based cohort study. SETTING: Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear. SUBJECTS AND METHODS: All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed. RESULTS: In total, 45,940 patients met criteria. Most were male (38,038, 82.8%), older than 60 years (23,456, 51.5%), and white (40,156, 87.4%), and lived in higher median income areas (>$48,000, 28,587, 62.2%). Two-thirds were HPV positive (31,007, 67.5%). HPV-negative disease was significantly more common in lower SES (<$38,000, 2937, 41.5%, P < .001) and among blacks (1784, 55.3%, P < .001). Median follow-up was 33 months. Five-year overall survival was 81.3% (95% CI, 80.5%-82.1%) and 59.6% (95% CI, 58.2%-61.0%) in HPV-positive and HPV-negative groups, respectively. In univariable and multivariable analyses controlling for HPV status, age, stage, and treatment, black race (hazard ratio [HR], 1.22; 95% CI, 1.11-1.34; P < .001) and low SES (HR, 1.58; 95% CI, 1.45-1.72; P < .001) were associated with worse survival. CONCLUSION: Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

Outcomes of carcinoma ex pleomorphic adenoma compared to de novo adenocarcinoma of major salivary glands.

BACKGROUND AND OBJECTIVES: Carcinoma ex pleomorphic adenoma (CXPA) is a rare disease of the major salivary glands that remains poorly characterized. Our objective was to compare the clinical outcomes of patients with CXPA of the major salivary glands to those with de novo adenocarcinomas. METHODS: Review of the NCDB between 2004 and 2016 to compare cases of CXPA and adenocarcinoma of major salivary glands. Demographics, clinical characteristics, and survival were analyzed. RESULTS: We identified 1181 patients with CXPA and 3326 patients with adenocarcinoma of major salivary glands. Adenocarcinomas presented with higher rates of nodal metastasis (54.7% vs. 30.4%, p < .001). Five-year survival of adenocarcinoma (55.8%) was worse than that of CXPA (68.5%, p < .001). When stratified by nodal status, there was no significant difference in 5-year survival between CXPA and adenocarcinoma node-negative (75.3% vs. 71.6%, respectively) and node-positive (40.4% vs. 36.1%, respectively) patients. CONCLUSIONS: CXPAs of the major salivary glands present at an earlier stage with lower rates of regional metastasis compared to adenocarcinomas. After controlling for lymph node metastases, the outcomes are quite similar.

Radiotherapy in Metastatic Oropharyngeal Cancer.

OBJECTIVES: The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy. METHODS: We queried the NCDB from 2004-2015 for metastatic OPSCC patients at diagnosis with known HPV-status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards model, and propensity score-matched analysis adjusting for demographic and disease-specific prognostic factors. RESULTS: Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV-status. Among these 556 patients, 49% were HPV-positive and 56% received head and neck radiotherapy. With a median follow-up of 17.5 months (IQR 6.0-163.4 months), radiotherapy was associated with significantly improved 1-year OS (67% vs 58%, log-rank P < .001) which remained significant on MVA (HR 0.78 95% CI 0.62-0.97 P = .029). In HPV-status subgroup analysis, a survival benefit was identified in HPV-positive patients (1-year OS 77% vs 67%, log-rank P < .001) but not in HPV-negative patients. Results were consistent on a propensity score-matched analysis of 212 HPV-positive matched patients (HR 0.66, 95% CI 0.49-0.83, P < .001). CONCLUSION: The survival of metastatic OPSCC remains limited. In this large series of patients with known HPV-status, head and neck radiotherapy was associated with longer survival in those with HPV-associated disease. These data could guide management of this challenging group of patients for head and neck cancer practitioners. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1847-E1853, 2021.

Treatment of Early Stage Tonsil Cancer in the Age of Human Papillomavirus-Associated Malignancies.

OBJECTIVE: To investigate the patterns of care and outcomes of treatment of early stage tonsil cancers, controlling for human papillomavirus (HPV) status. STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database (NCDB). METHODS: Review of the NCDB between 2010 and 2017 for all T1-2N0M0 tonsillar squamous cell carcinoma (SCC). Demographics, clinical characteristics, HPV status, treatment regimens, and survival were analyzed. RESULTS: A total of 4720 patients were identified with early stage SCC of the tonsil. Most were tested for HPV (2759 [58.5%]). Among tested patients, 1758 (63.7%) were positive for HPV and 1001 (36.3%) were negative for HPV. HPV-positive patients had higher 3-year survival compared to HPV-negative patients (93.2% vs 77.8%, P < .001). Among HPV-positive patients, there was no significant difference in survival between treatment cohorts. However, in the HPV-negative cohort, 3-year survival was higher in both bimodality surgical-based settings (tonsillectomy + neck dissection + radiotherapy, 86.0% vs chemoradiotherapy, 69.6%, P = .01) and for all surgical-based treatments when compared to nonsurgical management (84.6% vs 69.3%, P < .001). This difference was maintained in multivariable regression controlling for age, sex, comorbidities, clinical T stage, and treatments. In a subpopulation of HPV-negative patients propensity score matched by all factors significant in multivariable analysis, 3-year survival remained higher in the surgically treated group compared to the nonsurgically treated cohort (84.9% vs 67.1%, P < .001). CONCLUSIONS: Surgical- or radiation-based treatment resulted in similar survival in early stage HPV-positive tonsil cancer. Surgical-based treatments were associated with longer survival in HPV-negative cancers. These findings should be further investigated in a randomized prospective trial.