Human papillomavirus and survival of patients with sinonasal squamous cell carcinoma.

BACKGROUND: To the authors' knowledge, the question of whether human papillomavirus (HPV) infection is associated with outcomes in patients with sinonasal squamous cell carcinoma (SNSCC) is not well studied at this time. In the current study, the authors investigated patterns of HPV testing and its association with survival in patients with SNSCC using the National Cancer Data Base. METHODS: The authors selected all SNSCC cases diagnosed between 2010 and 2016. HPV testing practices, clinicodemographic factors, treatments, and survival were analyzed. Multivariable Cox regression and propensity score-matched survival analyses were performed. RESULTS: A total of 6458 SNSCC cases were identified. Of these, only 1523 cases (23.6%) were tested for HPV and included in the current study. The median patient age was 64 years and the majority had advanced stage tumors (overall AJCC stage III-IV, 721 patients; 62.1%). HPV-positive SNSCC comprised 31.5% (447 of 1418 cases) of the final study cohort. Among 15 hospitals that routinely tested nonoropharyngeal SCCs for HPV, the percentage of HPV-positive SNSCCs was smaller (24.6%; P = .04). Patients with HPV-positive SNSCC were younger (aged 60 years vs 65 years; P < .001), with tumors that were more likely to be high grade (55.3% vs 41.7%; P < .001), and attributed to the nasal cavity (62.2% vs 44.0%; P < .001). HPV-positive SNSCC was associated with significantly improved overall survival in multivariable regression analysis (hazard ratio, 0.45; 95% CI, 0.28-0.72 [P = .001]) and propensity score-matched (hazard ratio, 0.61; 95% CI, 0.38-0.96 [P = .03]) analyses controlling for clinicodemographic and treatment factors. CONCLUSIONS: Currently, only a minority of patients with SNSCC are tested for HPV. However, a sizable percentage of SNSCC cases may be HPV related; furthermore, HPV-positive SNSCC is associated with improved overall survival. Routine HPV testing may be warranted in patients with SNSCC.

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.

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.

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.

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.

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.

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.

Prognostic potential of mid-treatment nodal response in oropharyngeal squamous cell carcinoma.

BACKGROUND: We examine the prognostic implications of mid-course nodal response in oropharyngeal cancer (OPX) to radiation therapy. METHODS: In 44 patients with node-positive OPX undergoing concurrent chemoradiation, nodal volumes were measured on cone beam CTs from days 1, 10, 20, and 35. Nodal decrease (ND) was based on percent shrinkage from day 1. RESULTS: At a median follow-up of 17 months, the 2-year disease-free survival (DFS), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were 87%, 92%, 89%, and 92%, respectively. Patients with ND ≥43% at D20 had improved LRC (100% vs 78.4%, P = .03) compared to D20 ND <43%. On multivariate analysis, D20 ≥43% was independently prognostic for LRC (HR 1.17, P = .05). CONCLUSION: Patients with low-risk oropharynx cancer with ND of ≥43% by treatment day 20 had significantly improved LRC. The prognostic benefit of ND may assist in identifying candidates for treatment de-escalation.

Utilization and Survival of Postoperative Radiation or Chemoradiation for pT1-2N1M0 Head and Neck Cancer.

Objective To analyze the patterns of care and survival for pT1-2N1M0 head and neck cancer based on receipt of surgery alone, surgery + postoperative radiotherapy (S + RT), or surgery + postoperative chemoradiotherapy (S + CRT). Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods We queried the database for patients with stage pT1-2N1M0 squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx between 2004 and 2012 who were treated with surgery with negative margins and no extracapsular extension. Logistic regression was used to assess predictors of receipt of postoperative treatment. Overall survival was assessed by the Kaplan-Meier method, and Cox regression analysis identified covariates that affected it. Results There were 1598 patients included in this study: 566 (35.4%) received surgery alone; 726 (45.4%), S + RT; and 306 (19.1%), S + CRT. The 5-year overall survival was 68.8%, 74.0%, and 87.8%, respectively ( P = .009 comparing S + RT and surgery alone, P < .001 for all other comparisons). On multivariable logistic regression, academic centers were associated with a decreased likelihood of S + RT (odds ratio = 0.71) and S + CRT (odds ratio = 0.66). Multivariable Cox regression demonstrated no difference in survival for S + RT over surgery alone (hazard ratio = 0.88, 95% CI = 0.70-1.09, P = .24); however, there was a survival benefit associated with S + CRT (hazard ratio = 0.57, 95% CI = 0.39-0.81, P = .002). Conclusion Nearly 65% of patients with pT1-2N1 head and neck cancer with negative margins and no extracapsular extension received S + RT or S + CRT. Improvement in survival was noted only for patients who received S + CRT.

The effect of post-mastectomy radiation in women with one to three positive nodes enrolled on the control arm of BCIRG-005 at ten year follow-up.

BACKGROUND AND PURPOSE: We evaluated the effect of post-mastectomy radiation (PMRT) in 1-3 positive lymph nodes (LN) in patients who received uniform modern systemic therapy. MATERIALS AND METHODS: Cohort study using individual data collected for 1,649 node-positive women who received doxorubicin/cyclophosphamide with sequential docetaxel in 2000-2003 on the control arm of BCIRG-005. All women underwent mastectomy or lumpectomy and axillary LN dissection. PMRT was given at investigator's discretion. RESULTS: A total of 523 women with 1-3 positive LN underwent mastectomy and 39% (206/523) received PMRT. With a median follow-up of 10years, PMRT improved loco-regional control (LRC) from 91% to 98% (p=0.001) but had no effect on overall survival (OS) (84% vs. 86%, p=0.9). On multivariate analysis, PMRT improved local control (LC) (hazard ratio, 0.14; 95% CI, 0.03-0.62; p=0.01) and LRC (hazard ratio, 0.15; 95% CI, 0.04-0.50; p=0.002). PMRT did not significantly impact OS on multivariate analysis (hazard ratio, 0.91; 95% CI, 0.55-1.51; p=0.7). Results remained consistent with the use of propensity score analysis. CONCLUSIONS: In this cohort of patients with N1 disease treated with modern systemic therapy, PMRT improves LRC but has no effect on OS. The rates of OS were excellent, irrespective of adjuvant radiation.

Patterns of care and impact of brachytherapy boost utilization for squamous cell carcinoma of the base of tongue in a large, national cohort.

PURPOSE: The National Cancer Data Base was analyzed to evaluate the patterns of care and impact of brachytherapy (BT) boost on overall survival (OS) for patients with squamous cell carcinoma of the base of tongue. METHODS AND MATERIALS: Patients with nonmetastatic squamous cell carcinoma of the base of tongue between 2004 and 2012 who received concurrent external beam radiation therapy (EBRT) and chemotherapy with or without BT boost in the definitive setting were queried. Overall survival was assessed by the Kaplan-Meier method. Cox regression analysis was used to identify covariates that affected OS. RESULTS: There were 15,934 patients included in this study; 137 (0.9%) received EBRT + BT and the remaining received EBRT only. Median followup was 41.2 months. The utilization of BT boost declined from 2.1% in 2004 to 0.2% in 2012 (p < 0.0001), whereas intensity-modulated radiation therapy use increased from 22.8% in 2004 to 69.2% in 2012 (p < 0.0001). The three- and 5-year OS was 83.2% and 78.3% for patients receiving EBRT + BT compared with 77.4% and 69.0% for those receiving EBRT only (p = 0.03). The difference in survival was significantly better among patients with T3-4 tumors with EBRT + BT boost (p = 0.009) however, there was no survival benefit among patients with T1-2 tumors (p = 0.72). The analysis was repeated with patients who received intensity-modulated radiation therapy vs. EBRT with BT boost and the survival difference was sustained only for those with T3-4 tumors (p = 0.02). CONCLUSIONS: Brachytherapy boost has decreased in its utilization even though it was associated with favorable survival outcomes particularly among patients with higher T-stage tumors.