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Simple Summary: Immunotherapy represents the standard-of-care systemic therapy in patients with recurrent and metastatic head and neck cancer (HNC). However, these patients often present with local disease, which can affect quality of life, and local progression can lead to significant morbidity. Local response rates from immunotherapy alone are subpar. Thus, palliative radiation is often utilized in this scenario. 'QuadShot'(QS), a hypofractionated palliative radiation regimen, can provide symptomatic relief and local control and may potentiate the effects of immunotherapy. There have been no previous studies evaluating the combination of immunotherapy with QS. We found that the combination of QS with concurrent immunotherapy was well tolerated and significantly improved local control compared to QS alone. The median survival 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. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of oropharynx cancers usually requires radiation, chemotherapy, surgery, or a combination of all three. Although these treatments are effective, they can cause both short- and long-term side effects, particularly when more than one treatment option is used. Robotic surgery is now an option for patients with oropharynx cancers, but it is not clear how many patients will require additional treatment with radiation, or combined chemotherapy and radiation, after surgical treatment. In this study we used a large national database of oropharynx cancer patients and found that two-thirds of patients who were treated with robotic surgery required radiation therapy and one-third required chemotherapy with radiation. In addition, we found that the true tumor stage of the patients in this study was often higher than was initially thought prior to surgery. Finally, patients treated at high volume surgical centers were more likely to have more of their tumor removed compared to those at low volume facilities. Better survival quality of oropharynx cancer patients could be achieved by improving pre-surgical selection of patients so that the number of treatment modalities is reduced. 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. [ABSTRACT FROM AUTHOR]