Abstract
Simple SummaryRadiotherapy (RT) is an effective treatment for head and neck squamous cell carcinoma (HNSCC). Concurrent RT with high dose cisplatin (100 mg/m2, days 1, 22, and 42) is the standard of care (SOC) for non-operative HNSCC in curative settings, however, it is associated with both significant toxicities. In this review, we discussed the evidence of combination of anti-epidermal growth factor receptor, cetuximab, or immune checkpoint inhibitors (ICIs) with RT to compare with SOC. Cetuximab has been shown to be a less effective agent than cisplatin multiple recent trials, but it remains a reasonable alternative for those who are not fit for cisplatin. ICIs are active agents in recurrent and metastatic HNSCC. The role of ICIs with RT in the curative setting is yet to be defined. Multiple clinical trials are currently recruiting. Combining ICIs with stereotactic body radiotherapy (SBRT) is an attractive treatment in patients with oligometastatic or oligoprogressive HNSCC to boost the anti-tumor immune response.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.
Highlights
Each year, 700,000 new cases of head and neck squamous cell cancer (HNSCC) are diagnosed worldwide [1]
In a pivotal phase III trial, Bonner et al demonstrated improved locoregional control (LRC, HR 0.68; p = 0.005), progression free survival (PFS, HR 0.70; p = 0.006), and overall survival (OS, HR 0.74; p = 0.03) when cetuximab was added to definitive RT compared to RT alone for locally advanced head and neck squamous cell carcinoma (HNSCC) (LA-HNSCC)
The rationales for the combination are: (1) using immunotherapy as an alternative to cetuximab for those who are unfit for cisplatin chemotherapy; (2) treatment escalation in patients with high-risk disease; (3) as neoadjuvant therapy to select the responders for treatment de-escalation; (4) as an alternative systemic agent from cisplatin for patients with favorable prognosis
Summary
700,000 new cases of head and neck squamous cell cancer (HNSCC) are diagnosed worldwide [1]. A combination of cetuximab, an epidermal growth factor receptor antibody, with cisplatin and 5-FU chemotherapy was the first-line systemic therapy of choice for recurrent or metastatic HNSCC [10]. Patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV OPSCC) have substantially more favorable disease control rates and overall survival outcome [21,22,23] compared to their HPV-negative counterparts. Studies have focused on examining treatment de-escalation (with the intent of reducing treatment-related toxicities whilst preserving anti-tumor efficacy) in those with HPV OPSCC by combining radiotherapy with targeted therapy or immunotherapy to replace cytotoxic chemotherapy. We will describe the rationale of combining radiotherapy with epidermal growth factor receptor (EGFR) targeting and immunotherapy in locally advanced. Nasopharyngeal carcinoma, which represent a distinct subgroup of head and neck cancers, often associated with Epstein–Barr virus infection, are not included in this overview
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