Laryngeal squamous cell carcinoma is the second most common head and neck cancer. Its pathogenesis is strongly associated with smoking. The management of this disease is challenging and mandates multidisciplinary care. Currently, accepted treatment modalities include surgery, radiation therapy, and chemotherapy—all focused on improving survival while preserving organ function. Despite changes in smoking patterns resulting in a declining incidence of laryngeal cancer, the overall outcomes for this disease have not improved in the recent past, likely due to changes in treatment patterns and treatment-related toxicities. Here, we review emerging concepts and novel strategies in the use of radiation therapy in the management of laryngeal squamous cell carcinoma that could improve the relationship between tumor control and normal tissue damage (therapeutic ratio).

Background: Racial/ethnic (R/E) minorities with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. While disparities in patient outcomes for R/E minorities have been well documented, the specific drivers of the inferior outcomes remain poorly understood. Patients and Methods: This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database (NCDB) from 2000–2016. Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. The main outcome in this study was overall survival (OS). Univariate time-to-event survival analyses were performed using the Kaplan–Meier product limit estimates and the log-rank test to evaluate the differences between strata. Results: There were 304,138 patients with HNSCC identified in this study, of which 262,762 (86.3%) were White, 32,528 (10.6%) were Black, 6191 were Asian (2.0%), and 2657 were Native American/Other (0.9%). Black R/E minorities were more likely to be uninsured (9% vs. 5%, p < 0.0001), have Medicaid insurance (22% vs. 8%, p < 0.0001), be in a lower income quartile (<30,000, 42% vs. 13%, p < 0.0001), have metastatic disease (5% vs. 2%, p < 0.001), and have a total treatment time 6 days longer than White patients (median 107 vs. 101 days, p < 0.001). The 5-year OS for White, Black, Native American/Other, and Asian patients was 50.8%, 38.6%, 51.1%, and 55.8%, respectively. Among the oropharynx HNSCC patients, the 5-year OS rates in p16+ White, Black, and Asian patients were 65.7%, 39.4%%, and 55%, respectively. After a multivariate analysis, Black race was still associated with an inferior OS (HR:1.09, 95% CI: 1.03–1.15, p = 0.002). Conclusions: This large cohort study of HNSCC patients demonstrates that Black race is independently associated with worse OS, in part due to socioeconomic, clinical, and treatment-related factors.

Brain metastases are a devastating sequela of common primary cancers (e.g., lung, breast, and skin) and have limited effective therapeutic options. Previously, systemic chemotherapy failed to demonstrate significant benefit in patients with brain metastases, but in recent decades, targeted therapies and more recently immune checkpoint inhibitors (ICIs) have yielded promising results in preclinical and clinical studies. Furthermore, there is significant interest in harnessing the immunomodulatory effects of radiotherapy (RT) to synergize with ICIs. Herein, we discuss studies evaluating the impact of RT dose and fractionation on the immune response, early studies supporting the synergistic interaction between RT and ICIs, and ongoing clinical trials assessing the benefit of combination therapy in patients with brain metastases.

Trans-oral robotic surgery (TORS) has emerged as an important surgical treatment option in the management of human papillomavirus (HPV)-positive and -negative oropharynx cancer. However, treatment selection is paramount to ensure that patients will not require multimodality adjuvant therapy. In this study, we determined predictors of adjuvant therapy in TORS-treated patients. The National Cancer Database (NCDB) was used to identify patients with newly diagnosed clinical T1-T4, N0-N3 oropharyngeal squamous cell carcinoma who underwent TORS between 2010–2016. Kaplan–Meier survival analysis was used to estimate overall survival (OS). A total of 2999 patients were studied, and the five-year OS for the entire cohort was 82.5%, and for HPV-positive and -negative cohorts it was 88.3% and 67.9%, respectively (p < 0.001). Among all patients treated with TORS, 35.1% of patients received no additional treatment, 33.5% received adjuvant radiation alone (RT), and 31.3% received adjuvant chemoradiation. The N stage was pathologically upstaged in 629 (20.9%) patients after TORS. Patients treated at higher-volume centers were more likely to have negative surgical margins (OR: 0.96, 95% CI: 0.94, 0.98, p < 0.001), but this did not influence the receipt of adjuvant therapy. The high rate of adjuvant multimodality treatment after TORS suggests a need for improved patient selection. Limitations of this study, including lack of data on loco-regional control, progression free survival, acute and late toxicities, and utilization of pretreatment PET/CT imaging, should be addressed in future studies.

Objectives: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. ‘QuadShot’ (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC. Materials and Methods: We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS. Results: Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9–77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60–70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073–0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups. Conclusions: The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.