Contralateral nodal failures in oropharyngeal cancers after TORS and unilateral neck management: a retrospective study

Background Report the incidence of contralateral nodal failure rates in well-lateralized oropharyngeal carcinoma treated with upfront surgery and unilateral neck management. Methods Lateralized oropharyngeal carcinomas treated with upfront surgery using transoral robotic surgery (TORS) and unilateral neck management (unilateral neck dissection ± unilateral radiation treatment) were identified. Primary endpoint was contralateral regional control (CRC). Secondary endpoints were local control (LC), and overall survival (OS). Results Thirty-two patients were included. Pathologic T categories included 66% pT1, 31% pT2 and 3% pT3. Nodal diseases comprised 41% N0 and 47% N1 (AJCC 8th). Twenty-three (72%) patients had HPV related tumors. 3-years CRC, LC and OS were 100%, 96% (89–100) and 96% (CI 89–100). One patient developed a second primary with contralateral nodal disease. Only one patient died from another primary cancer. Conclusion In selected patients with lateralized oropharyngeal cancer, treatment with TORS and ipsilateral management of the neck may be oncologically safe without significant risk of contralateral failure. Level of evidence: Level 2. Graphical abstract

Recent Research on Combination of Radiotherapy with Targeted Therapy or Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Review for Radiation Oncologists

Radiotherapy plays an important role of managing head and neck squamous cell carcinoma (HNSCC). Concurrent radiotherapy with radiosensitizing cisplastin chemotherapy is the standard of care (SOC) for non-operable locally advanced HNSCC. Cetuximab, a monoclonal antibody of epidermal growth factor receptor, was the most extensively studied targeted therapy as a chemo-sparing agent that was used concurrently with radiotherapy. Immunotherapy is used in the treatment of metastatic HNSCC. There is evidence to support the synergistic effect when combining radiotherapy with immunotherapy to potentiate anti-tumor immune response. There has been increasing interest to incorporate immune checkpoint inhibitor (ICI) with radiotherapy in the curative setting for HNSCC. In this review, we discuss the latest evidence that supports concurrent radiotherapy with cisplatin which remains the SOC for locally advanced HNSCC (LA-HNSCC). Cetuximab is suitable for patients who are not fit for cisplatin. We then summarize the clinical trials that incorporate ICI with radiotherapy for LA-HNSCC in concurrent, neoadjuvant, and adjuvant settings. We also discuss the potential of combining immunotherapy with radiotherapy as a treatment de-escalating strategy in HPV-associated oropharyngeal carcinoma. Finally, the pre-clinical and clinical evidence of the abscopal effect when combining stereotactic body radiotherapy with ICIs is presented.

Swallowing Function Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharyngeal Carcinoma: A 2-Year Follow-up

Objective To evaluate 2-year follow-up swallowing function in patients with human papillomavirus–related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) who completed neoadjuvant chemotherapy and transoral robotic surgery (NAC+S) Study Design Retrospective analysis of patients with OPSCC treated with NAC+S between 2010 and 2021. Setting A single academic institution. Methods This is a cross-sectional study of patient-reported swallowing function, assessed with the MD Anderson Dysphagia Inventory (MDADI) at least 2 years after completion of treatment. The inclusion criteria are patients with HPV+ OPSCC who underwent NAC+S at least 2 years ago. Those requiring adjuvant radiation or chemoradiation or experiencing relapse were excluded from the study. Results Completed MDADIs were received from 37 patients at a median 3.8 years posttreatment (interquartile range, 2.0-8.6 years). Of those, 94.6% (n = 35) were male and 81.1% (n = 30) were White. The median age at OPSCC diagnosis was 59.0 years (interquartile range, 41-80 years). The most frequent primary subsite of OPSCC was the base of the tongue (n = 20, 54.1%), followed by the tonsils (n = 16, 43.2%). In addition, 75.7% (n = 28) had stage IVa disease (TNM seventh edition), and 29 (78.4%) had scores ≥80, classified as optimal function. When compared with patients who received bilateral neck dissection, patients who received unilateral neck dissection were associated with an age <65 years old ( P = .036) and lower clinical TNM stage ( P = .04), as well as higher composite, emotional, functional, and physical MDADI scores ( P = .017, .046, .013, and .05, respectively). Conclusion Patients with OPSCC who were treated with NAC+S achieved satisfactory long-term swallowing outcomes. Unilateral neck dissection was significantly associated with higher MDADI scores in this patient cohort.

Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus–Positive Oropharyngeal Carcinoma

PURPOSE Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)–positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models. METHODS Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102 ) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model. RESULTS The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster ( P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster. CONCLUSION The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.